Skip to main content
Erschienen in: Cancer and Metastasis Reviews 2/2008

01.06.2008

The tyrosine phosphatase Shp2 (PTPN11) in cancer

verfasst von: Gordon Chan, Demetrios Kalaitzidis, Benjamin G. Neel

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 2/2008

Einloggen, um Zugang zu erhalten

Abstract

Diverse cellular processes are regulated by tyrosyl phosphorylation, which is controlled by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). De-regulated tyrosyl phosphorylation, evoked by gain-of-function mutations and/or over-expression of PTKs, contributes to the pathogenesis of many cancers and other human diseases. PTPs, because they oppose the action of PTKs, had been considered to be prime suspects for potential tumor suppressor genes. Surprisingly, few, if any, tumor suppressor PTPs have been identified. However, the Src homology-2 domain-containing phosphatase Shp2 (encoded by PTPN11) is a bona fide proto-oncogene. Germline mutations in PTPN11 cause Noonan and LEOPARD syndromes, whereas somatic PTPN11 mutations occur in several types of hematologic malignancies, most notably juvenile myelomonocytic leukemia and, more rarely, in solid tumors. Shp2 also is an essential component in several other oncogene signaling pathways. Elucidation of the events underlying Shp2-evoked transformation may provide new insights into oncogenic mechanisms and novel targets for anti-cancer therapy.
Literatur
1.
Zurück zum Zitat Mohi, M. G., & Neel, B. G. (2007). The role of Shp2 (PTPN11) in cancer. Current Opinion in Genetics & Development, 17(1), 23–30.CrossRef Mohi, M. G., & Neel, B. G. (2007). The role of Shp2 (PTPN11) in cancer. Current Opinion in Genetics & Development, 17(1), 23–30.CrossRef
2.
Zurück zum Zitat Neel, B. G., Gu, H., & Pao, L. (2003). The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends in Biochemical Sciences, 28(6), 284–293.PubMedCrossRef Neel, B. G., Gu, H., & Pao, L. (2003). The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends in Biochemical Sciences, 28(6), 284–293.PubMedCrossRef
3.
Zurück zum Zitat Pao, L. I., Badour, K., Siminovitch, K. A., & Neel, B. G. (2007). Nonreceptor protein-tyrosine phosphatases in immune cell signaling. Annual Review of Immunology, 25, 473–523.PubMedCrossRef Pao, L. I., Badour, K., Siminovitch, K. A., & Neel, B. G. (2007). Nonreceptor protein-tyrosine phosphatases in immune cell signaling. Annual Review of Immunology, 25, 473–523.PubMedCrossRef
4.
Zurück zum Zitat Feng, G. S. (1999). Shp-2 tyrosine phosphatase: signaling one cell or many. Experimental Cell Research, 253(1), 47–54.PubMedCrossRef Feng, G. S. (1999). Shp-2 tyrosine phosphatase: signaling one cell or many. Experimental Cell Research, 253(1), 47–54.PubMedCrossRef
5.
Zurück zum Zitat Chan, R. J., & Feng, G. S. (2007). PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase. Blood, 109(3), 862–867.PubMedCrossRef Chan, R. J., & Feng, G. S. (2007). PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase. Blood, 109(3), 862–867.PubMedCrossRef
6.
Zurück zum Zitat Tartaglia, M., Mehler, E. L., Goldberg, R., Zampino, G., Brunner, H. G., Kremer, H., et al. (2001). Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nature Genetics, 29(4), 465–468.PubMedCrossRef Tartaglia, M., Mehler, E. L., Goldberg, R., Zampino, G., Brunner, H. G., Kremer, H., et al. (2001). Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nature Genetics, 29(4), 465–468.PubMedCrossRef
7.
Zurück zum Zitat Tartaglia, M., & Gelb, B. D. (2005). Noonan syndrome and related disorders: Genetics and pathogenesis. Annual Review of Genomics and Human Genetics, 6, 45–68.PubMedCrossRef Tartaglia, M., & Gelb, B. D. (2005). Noonan syndrome and related disorders: Genetics and pathogenesis. Annual Review of Genomics and Human Genetics, 6, 45–68.PubMedCrossRef
8.
Zurück zum Zitat Tartaglia, M., Niemeyer, C. M., Shannon, K. M., & Loh, M. L. (2004). SHP-2 and myeloid malignancies. Current Opinion in Hematology, 11(1), 44–50.PubMedCrossRef Tartaglia, M., Niemeyer, C. M., Shannon, K. M., & Loh, M. L. (2004). SHP-2 and myeloid malignancies. Current Opinion in Hematology, 11(1), 44–50.PubMedCrossRef
9.
Zurück zum Zitat Tartaglia, M., Niemeyer, C. M., Fragale, A., Song, X., Buechner, J., Jung, A., et al. (2003). Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nature Genetics, 34(2), 148–150.PubMedCrossRef Tartaglia, M., Niemeyer, C. M., Fragale, A., Song, X., Buechner, J., Jung, A., et al. (2003). Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nature Genetics, 34(2), 148–150.PubMedCrossRef
10.
Zurück zum Zitat Loh, M. L., Vattikuti, S., Schubbert, S., Reynolds, M. G., Carlson, E., Lieuw, K. H., et al. (2004). Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis. Blood, 103(6), 2325–2331.PubMedCrossRef Loh, M. L., Vattikuti, S., Schubbert, S., Reynolds, M. G., Carlson, E., Lieuw, K. H., et al. (2004). Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis. Blood, 103(6), 2325–2331.PubMedCrossRef
11.
Zurück zum Zitat Neel, B., Gu, H., & Pao, L. (2003). SH2 domain-containing protein tyrosine phosphatases. In R. A. Bradshaw, & E. A. Dennis (Eds.) Handbook cell signaling pp. 707–730. Amsterdam: Elsevier.CrossRef Neel, B., Gu, H., & Pao, L. (2003). SH2 domain-containing protein tyrosine phosphatases. In R. A. Bradshaw, & E. A. Dennis (Eds.) Handbook cell signaling pp. 707–730. Amsterdam: Elsevier.CrossRef
12.
Zurück zum Zitat Gelb, B. D., & Tartaglia, M. (2006). Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction. Human Molecular Genetics, 15(Spec No 2), R220–226.PubMedCrossRef Gelb, B. D., & Tartaglia, M. (2006). Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction. Human Molecular Genetics, 15(Spec No 2), R220–226.PubMedCrossRef
13.
Zurück zum Zitat Tonks, N. K., & Neel, B. G. (2001). Combinatorial control of the specificity of protein tyrosine phosphatases. Current Opinion in Cell Biology, 13(2), 182–195.PubMedCrossRef Tonks, N. K., & Neel, B. G. (2001). Combinatorial control of the specificity of protein tyrosine phosphatases. Current Opinion in Cell Biology, 13(2), 182–195.PubMedCrossRef
14.
Zurück zum Zitat Van Vactor, D., O’Reilly, A. M., & Neel, B. G. (1998). Genetic analysis of protein tyrosine phosphatases. Current Opinion in Genetics & Development, 8(1), 112–126.CrossRef Van Vactor, D., O’Reilly, A. M., & Neel, B. G. (1998). Genetic analysis of protein tyrosine phosphatases. Current Opinion in Genetics & Development, 8(1), 112–126.CrossRef
15.
Zurück zum Zitat Araki, T., Nawa, H., & Neel, B. G. (2003). Tyrosyl phosphorylation of Shp2 is required for normal ERK activation in response to some, but not all, growth factors. Journal of Biological Chemistry, 278(43), 41677–41684.PubMedCrossRef Araki, T., Nawa, H., & Neel, B. G. (2003). Tyrosyl phosphorylation of Shp2 is required for normal ERK activation in response to some, but not all, growth factors. Journal of Biological Chemistry, 278(43), 41677–41684.PubMedCrossRef
16.
Zurück zum Zitat Hof, P., Pluskey, S., Dhe-Paganon, S., Eck, M. J., & Shoelson, S. E. (1998). Crystal structure of the tyrosine phosphatase SHP-2. Cell, 92(4), 441–450.PubMedCrossRef Hof, P., Pluskey, S., Dhe-Paganon, S., Eck, M. J., & Shoelson, S. E. (1998). Crystal structure of the tyrosine phosphatase SHP-2. Cell, 92(4), 441–450.PubMedCrossRef
17.
Zurück zum Zitat Barford, D., & Neel, B. G. (1998). Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2. Structure, 6(3), 249–254.PubMedCrossRef Barford, D., & Neel, B. G. (1998). Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2. Structure, 6(3), 249–254.PubMedCrossRef
18.
Zurück zum Zitat O’Reilly, A. M., Pluskey, S., Shoelson, S. E., & Neel, B. G. (2000). Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps. Molecular and Cellular Biology, 20(1), 299–311.PubMed O’Reilly, A. M., Pluskey, S., Shoelson, S. E., & Neel, B. G. (2000). Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps. Molecular and Cellular Biology, 20(1), 299–311.PubMed
19.
Zurück zum Zitat Zhang, S. Q., Yang, W., Kontaridis, M. I., Bivona, T. G., Wen, G., Araki, T., et al. (2004). Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Molecular Cell, 13(3), 341–355.PubMedCrossRef Zhang, S. Q., Yang, W., Kontaridis, M. I., Bivona, T. G., Wen, G., Araki, T., et al. (2004). Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Molecular Cell, 13(3), 341–355.PubMedCrossRef
20.
Zurück zum Zitat Ren, Y., Meng, S., Mei, L., Zhao, Z. J., Jove, R., & Wu, J. (2004). Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation in response to epidermal growth factor. Journal of Biological Chemistry, 279(9), 8497–8505.PubMedCrossRef Ren, Y., Meng, S., Mei, L., Zhao, Z. J., Jove, R., & Wu, J. (2004). Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation in response to epidermal growth factor. Journal of Biological Chemistry, 279(9), 8497–8505.PubMedCrossRef
21.
Zurück zum Zitat Bertotti, A., Comoglio, P. M., & Trusolino, L. (2006). Beta4 integrin activates a Shp2-Src signaling pathway that sustains HGF-induced anchorage-independent growth. Journal of Cell Biology, 175(6), 993–1003.PubMedCrossRef Bertotti, A., Comoglio, P. M., & Trusolino, L. (2006). Beta4 integrin activates a Shp2-Src signaling pathway that sustains HGF-induced anchorage-independent growth. Journal of Cell Biology, 175(6), 993–1003.PubMedCrossRef
22.
Zurück zum Zitat Klinghoffer, R. A., & Kazlauskas, A. (1995). Identification of a putative Syp substrate, the PDGF beta receptor. Journal of Biological Chemistry, 270(38), 22208–22217.PubMedCrossRef Klinghoffer, R. A., & Kazlauskas, A. (1995). Identification of a putative Syp substrate, the PDGF beta receptor. Journal of Biological Chemistry, 270(38), 22208–22217.PubMedCrossRef
23.
Zurück zum Zitat Agazie, Y. M., & Hayman, M. J. (2003). Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling. Molecular and Cellular Biology, 23(21), 7875–7886.PubMedCrossRef Agazie, Y. M., & Hayman, M. J. (2003). Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling. Molecular and Cellular Biology, 23(21), 7875–7886.PubMedCrossRef
24.
Zurück zum Zitat Cleghon, V., Feldmann, P., Ghiglione, C., Copeland, T. D., Perrimon, N., Hughes, D. A., et al. (1998). Opposing actions of CSW and RasGAP modulate the strength of Torso RTK signaling in the Drosophila terminal pathway. Molecular Cell, 2(6), 719–727.PubMedCrossRef Cleghon, V., Feldmann, P., Ghiglione, C., Copeland, T. D., Perrimon, N., Hughes, D. A., et al. (1998). Opposing actions of CSW and RasGAP modulate the strength of Torso RTK signaling in the Drosophila terminal pathway. Molecular Cell, 2(6), 719–727.PubMedCrossRef
25.
Zurück zum Zitat Hanafusa, H., Torii, S., Yasunaga, T., Matsumoto, K., & Nishida, E. (2004). Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. Journal of Biological Chemistry, 279(22), 22992–22995.PubMedCrossRef Hanafusa, H., Torii, S., Yasunaga, T., Matsumoto, K., & Nishida, E. (2004). Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. Journal of Biological Chemistry, 279(22), 22992–22995.PubMedCrossRef
26.
Zurück zum Zitat Jarvis, L. A., Toering, S. J., Simon, M. A., Krasnow, M. A., & Smith-Bolton, R. K. (2006). Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases. Development, 133(6), 1133–1142.PubMedCrossRef Jarvis, L. A., Toering, S. J., Simon, M. A., Krasnow, M. A., & Smith-Bolton, R. K. (2006). Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases. Development, 133(6), 1133–1142.PubMedCrossRef
27.
Zurück zum Zitat Zhang, S. Q., Tsiaras, W. G., Araki, T., Wen, G., Minichiello, L., Klein, R., et al. (2002). Receptor-specific regulation of phosphatidylinositol 3’′-kinase activation by the protein tyrosine phosphatase Shp2. Molecular and Cellular Biology, 22(12), 4062–4072.PubMedCrossRef Zhang, S. Q., Tsiaras, W. G., Araki, T., Wen, G., Minichiello, L., Klein, R., et al. (2002). Receptor-specific regulation of phosphatidylinositol 3’′-kinase activation by the protein tyrosine phosphatase Shp2. Molecular and Cellular Biology, 22(12), 4062–4072.PubMedCrossRef
28.
Zurück zum Zitat Mattoon, D. R., Lamothe, B., Lax, I., & Schlessinger, J. (2004). The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K/Akt cell survival pathway. BMC Biol, 2, 24.PubMedCrossRef Mattoon, D. R., Lamothe, B., Lax, I., & Schlessinger, J. (2004). The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K/Akt cell survival pathway. BMC Biol, 2, 24.PubMedCrossRef
29.
Zurück zum Zitat Shi, Z. Q., Lu, W., & Feng, G. S. (1998). The Shp-2 tyrosine phosphatase has opposite effects in mediating the activation of extracellular signal-regulated and c-Jun NH2-terminal mitogen-activated protein kinases. Journal of Biological Chemistry, 273(9), 4904–4908.PubMedCrossRef Shi, Z. Q., Lu, W., & Feng, G. S. (1998). The Shp-2 tyrosine phosphatase has opposite effects in mediating the activation of extracellular signal-regulated and c-Jun NH2-terminal mitogen-activated protein kinases. Journal of Biological Chemistry, 273(9), 4904–4908.PubMedCrossRef
30.
Zurück zum Zitat You, M., Flick, L. M., Yu, D., & Feng, G. S. (2001). Modulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor. Journal of Experimental Medicine, 193(1), 101–110.PubMedCrossRef You, M., Flick, L. M., Yu, D., & Feng, G. S. (2001). Modulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor. Journal of Experimental Medicine, 193(1), 101–110.PubMedCrossRef
31.
Zurück zum Zitat Schoenwaelder, S. M., Petch, L. A., Williamson, D., Shen, R., Feng, G. S., & Burridge, K. (2000). The protein tyrosine phosphatase Shp-2 regulates RhoA activity. Current Biology, 10(23), 1523–1526.PubMedCrossRef Schoenwaelder, S. M., Petch, L. A., Williamson, D., Shen, R., Feng, G. S., & Burridge, K. (2000). The protein tyrosine phosphatase Shp-2 regulates RhoA activity. Current Biology, 10(23), 1523–1526.PubMedCrossRef
32.
Zurück zum Zitat Kontaridis, M. I., Eminaga, S., Fornaro, M., Zito, C. I., Sordella, R., Settleman, J., et al. (2004). SHP-2 positively regulates myogenesis by coupling to the Rho GTPase signaling pathway. Molecular and Cellular Biology, 24(12), 5340–5352.PubMedCrossRef Kontaridis, M. I., Eminaga, S., Fornaro, M., Zito, C. I., Sordella, R., Settleman, J., et al. (2004). SHP-2 positively regulates myogenesis by coupling to the Rho GTPase signaling pathway. Molecular and Cellular Biology, 24(12), 5340–5352.PubMedCrossRef
33.
Zurück zum Zitat Uhlen, P., Burch, P. M., Zito, C. I., Estrada, M., Ehrlich, B. E., & Bennett, A. M. (2006). Gain-of-function/Noonan syndrome SHP-2/Ptpn11 mutants enhance calcium oscillations and impair NFAT signaling. Proceedings of the National Academy of Sciences of the United States of America, 103(7), 2160–2165.PubMedCrossRef Uhlen, P., Burch, P. M., Zito, C. I., Estrada, M., Ehrlich, B. E., & Bennett, A. M. (2006). Gain-of-function/Noonan syndrome SHP-2/Ptpn11 mutants enhance calcium oscillations and impair NFAT signaling. Proceedings of the National Academy of Sciences of the United States of America, 103(7), 2160–2165.PubMedCrossRef
34.
Zurück zum Zitat Walter, A. O., Peng, Z. Y., & Cartwright, C. A. (1999). The Shp-2 tyrosine phosphatase activates the Src tyrosine kinase by a non-enzymatic mechanism. Oncogene, 18(11), 1911–1920.PubMedCrossRef Walter, A. O., Peng, Z. Y., & Cartwright, C. A. (1999). The Shp-2 tyrosine phosphatase activates the Src tyrosine kinase by a non-enzymatic mechanism. Oncogene, 18(11), 1911–1920.PubMedCrossRef
35.
Zurück zum Zitat Yu, W. M., Hawley, T. S., Hawley, R. G., & Qu, C. K. (2003). Catalytic-dependent and -independent roles of SHP-2 tyrosine phosphatase in interleukin-3 signaling. Oncogene, 22(38), 5995–6004.PubMedCrossRef Yu, W. M., Hawley, T. S., Hawley, R. G., & Qu, C. K. (2003). Catalytic-dependent and -independent roles of SHP-2 tyrosine phosphatase in interleukin-3 signaling. Oncogene, 22(38), 5995–6004.PubMedCrossRef
36.
Zurück zum Zitat Schubbert, S., Zenker, M., Rowe, S. L., Boll, S., Klein, C., Bollag, G., et al. (2006). Germline KRAS mutations cause Noonan syndrome. Nature Genetics, 38(3), 331–336.PubMedCrossRef Schubbert, S., Zenker, M., Rowe, S. L., Boll, S., Klein, C., Bollag, G., et al. (2006). Germline KRAS mutations cause Noonan syndrome. Nature Genetics, 38(3), 331–336.PubMedCrossRef
37.
Zurück zum Zitat Carta, C., Pantaleoni, F., Bocchinfuso, G., Stella, L., Vasta, I., Sarkozy, A., et al. (2006). Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. American Journal of Human Genetics, 79(1), 129–135.PubMedCrossRef Carta, C., Pantaleoni, F., Bocchinfuso, G., Stella, L., Vasta, I., Sarkozy, A., et al. (2006). Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. American Journal of Human Genetics, 79(1), 129–135.PubMedCrossRef
38.
Zurück zum Zitat Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., et al. (2007). Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nature Genetics, 39(1), 70–74.PubMedCrossRef Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., et al. (2007). Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nature Genetics, 39(1), 70–74.PubMedCrossRef
39.
Zurück zum Zitat Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., et al. (2007). Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nature Genetics, 39(1), 75–79.PubMedCrossRef Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., et al. (2007). Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nature Genetics, 39(1), 75–79.PubMedCrossRef
40.
Zurück zum Zitat Razzaque, M. A., Nishizawa, T., Komoike, Y., Yagi, H., Furutani, M., Amo, R., et al. (2007). Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nature Genetics, 39, 1013–1017.PubMedCrossRef Razzaque, M. A., Nishizawa, T., Komoike, Y., Yagi, H., Furutani, M., Amo, R., et al. (2007). Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nature Genetics, 39, 1013–1017.PubMedCrossRef
41.
Zurück zum Zitat Pandit, B., Sarkozy, A., Pennacchio, L. A., Carta, C., Oishi, K., Martinelli, S., et al. (2007). Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nature Genetics, 39, 1007–1012.PubMedCrossRef Pandit, B., Sarkozy, A., Pennacchio, L. A., Carta, C., Oishi, K., Martinelli, S., et al. (2007). Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nature Genetics, 39, 1007–1012.PubMedCrossRef
42.
Zurück zum Zitat Tartaglia, M., Martinelli, S., Iavarone, I., Cazzaniga, G., Spinelli, M., Giarin, E., et al. (2005). Somatic PTPN11 mutations in childhood acute myeloid leukaemia. British Journal of Haematology, 129(3), 333–339.PubMedCrossRef Tartaglia, M., Martinelli, S., Iavarone, I., Cazzaniga, G., Spinelli, M., Giarin, E., et al. (2005). Somatic PTPN11 mutations in childhood acute myeloid leukaemia. British Journal of Haematology, 129(3), 333–339.PubMedCrossRef
43.
Zurück zum Zitat Bentires-Alj, M., Paez, J. G., David, F. S., Keilhack, H., Halmos, B., Naoki, K., et al. (2004). Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Research, 64(24), 8816–8820.PubMedCrossRef Bentires-Alj, M., Paez, J. G., David, F. S., Keilhack, H., Halmos, B., Naoki, K., et al. (2004). Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Research, 64(24), 8816–8820.PubMedCrossRef
44.
Zurück zum Zitat Loh, M. L., Reynolds, M. G., Vattikuti, S., Gerbing, R. B., Alonzo, T. A., Carlson, E., et al. (2004). PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children’s Cancer Group. Leukemia, 18(11), 1831–1834.PubMedCrossRef Loh, M. L., Reynolds, M. G., Vattikuti, S., Gerbing, R. B., Alonzo, T. A., Carlson, E., et al. (2004). PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children’s Cancer Group. Leukemia, 18(11), 1831–1834.PubMedCrossRef
45.
Zurück zum Zitat Tartaglia, M., Martinelli, S., Cazzaniga, G., Cordeddu, V., Iavarone, I., Spinelli, M., et al. (2004). Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. Blood, 104(2), 307–313.PubMedCrossRef Tartaglia, M., Martinelli, S., Cazzaniga, G., Cordeddu, V., Iavarone, I., Spinelli, M., et al. (2004). Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. Blood, 104(2), 307–313.PubMedCrossRef
46.
Zurück zum Zitat Yamamoto, T., Isomura, M., Xu, Y., Liang, J., Yagasaki, H., Kamachi, Y., et al. (2006). PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia. Leukemia Research, 30(9), 1085–1089.PubMedCrossRef Yamamoto, T., Isomura, M., Xu, Y., Liang, J., Yagasaki, H., Kamachi, Y., et al. (2006). PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia. Leukemia Research, 30(9), 1085–1089.PubMedCrossRef
47.
Zurück zum Zitat Martinelli, S., Carta, C., Flex, E., Binni, F., Cordisco, E. L., Moretti, S., et al. (2006). Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors. Cancer Genetics and Cytogenetics, 166(2), 124–129.PubMedCrossRef Martinelli, S., Carta, C., Flex, E., Binni, F., Cordisco, E. L., Moretti, S., et al. (2006). Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors. Cancer Genetics and Cytogenetics, 166(2), 124–129.PubMedCrossRef
48.
Zurück zum Zitat Sjoblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., et al. (2006). The consensus coding sequences of human breast and colorectal cancers. Science, 314(5797), 268–274.PubMedCrossRef Sjoblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., et al. (2006). The consensus coding sequences of human breast and colorectal cancers. Science, 314(5797), 268–274.PubMedCrossRef
49.
Zurück zum Zitat Tartaglia, M., Kalidas, K., Shaw, A., Song, X., Musat, D. L., van der Burgt, I., et al. (2002). PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype–phenotype correlation, and phenotypic heterogeneity. American Journal of Human Genetics, 70(6), 1555–1563.PubMedCrossRef Tartaglia, M., Kalidas, K., Shaw, A., Song, X., Musat, D. L., van der Burgt, I., et al. (2002). PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype–phenotype correlation, and phenotypic heterogeneity. American Journal of Human Genetics, 70(6), 1555–1563.PubMedCrossRef
50.
Zurück zum Zitat Kosaki, K., Suzuki, T., Muroya, K., Hasegawa, T., Sato, S., Matsuo, N., et al. (2002). PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome. Journal of Clinical Endocrinology and Metabolism, 87(8), 3529–3533.PubMedCrossRef Kosaki, K., Suzuki, T., Muroya, K., Hasegawa, T., Sato, S., Matsuo, N., et al. (2002). PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome. Journal of Clinical Endocrinology and Metabolism, 87(8), 3529–3533.PubMedCrossRef
51.
Zurück zum Zitat Keilhack, H., David, F. S., McGregor, M., Cantley, L. C., & Neel, B. G. (2005). Diverse biochemical properties of Shp2 mutants. Implications for disease phenotypes. Journal of Biological Chemistry, 280(35), 30984–30993.PubMedCrossRef Keilhack, H., David, F. S., McGregor, M., Cantley, L. C., & Neel, B. G. (2005). Diverse biochemical properties of Shp2 mutants. Implications for disease phenotypes. Journal of Biological Chemistry, 280(35), 30984–30993.PubMedCrossRef
52.
Zurück zum Zitat Niihori, T., Aoki, Y., Ohashi, H., Kurosawa, K., Kondoh, T., Ishikiriyama, S., et al. (2005). Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia. Journal of Human Genetics, 50(4), 192–202.PubMedCrossRef Niihori, T., Aoki, Y., Ohashi, H., Kurosawa, K., Kondoh, T., Ishikiriyama, S., et al. (2005). Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia. Journal of Human Genetics, 50(4), 192–202.PubMedCrossRef
53.
Zurück zum Zitat Tartaglia, M., Martinelli, S., Stella, L., Bocchinfuso, G., Flex, E., Cordeddu, V., et al. (2006). Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. American Journal of Human Genetics, 78(2), 279–290.PubMedCrossRef Tartaglia, M., Martinelli, S., Stella, L., Bocchinfuso, G., Flex, E., Cordeddu, V., et al. (2006). Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. American Journal of Human Genetics, 78(2), 279–290.PubMedCrossRef
54.
Zurück zum Zitat Araki, T., Mohi, M. G., Ismat, F. A., Bronson, R. T., Williams, I. R., Kutok, J. L., et al. (2004). Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nature Medicine, 10(8), 849–857.PubMedCrossRef Araki, T., Mohi, M. G., Ismat, F. A., Bronson, R. T., Williams, I. R., Kutok, J. L., et al. (2004). Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nature Medicine, 10(8), 849–857.PubMedCrossRef
55.
Zurück zum Zitat Kontaridis, M. I., Swanson, K. D., David, F. S., Barford, D., & Neel, B. G. (2006). PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. Journal of Biological Chemistry, 281(10), 6785–6792.PubMedCrossRef Kontaridis, M. I., Swanson, K. D., David, F. S., Barford, D., & Neel, B. G. (2006). PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. Journal of Biological Chemistry, 281(10), 6785–6792.PubMedCrossRef
56.
Zurück zum Zitat Hanna, N., Montagner, A., Lee, W. H., Miteva, M., Vidal, M., Vidaud, M., et al. (2006). Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1. FEBS Letters, 580(10), 2477–2482.PubMedCrossRef Hanna, N., Montagner, A., Lee, W. H., Miteva, M., Vidal, M., Vidaud, M., et al. (2006). Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1. FEBS Letters, 580(10), 2477–2482.PubMedCrossRef
57.
Zurück zum Zitat Conti, E., Dottorini, T., Sarkozy, A., Tiller, G. E., Esposito, G., Pizzuti, A., et al. (2003). A novel PTPN11 mutation in LEOPARD syndrome. Human Mutation, 21(6), 654.PubMedCrossRef Conti, E., Dottorini, T., Sarkozy, A., Tiller, G. E., Esposito, G., Pizzuti, A., et al. (2003). A novel PTPN11 mutation in LEOPARD syndrome. Human Mutation, 21(6), 654.PubMedCrossRef
58.
Zurück zum Zitat Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K., Kato, R., et al. (2007). Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nature Genetics, 39(9), 1120–1126.PubMedCrossRef Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K., Kato, R., et al. (2007). Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nature Genetics, 39(9), 1120–1126.PubMedCrossRef
59.
Zurück zum Zitat Sarkozy, A., Conti, E., Digilio, M. C., Marino, B., Morini, E., Pacileo, G., et al. (2004). Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome. Journal of Medical Genetics, 41(5), e68.PubMedCrossRef Sarkozy, A., Conti, E., Digilio, M. C., Marino, B., Morini, E., Pacileo, G., et al. (2004). Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome. Journal of Medical Genetics, 41(5), e68.PubMedCrossRef
60.
Zurück zum Zitat Ucar, C., Calyskan, U., Martini, S., & Heinritz, W. (2006). Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive). Journal of Pediatric Hematology Oncology, 28(3), 123–125.CrossRef Ucar, C., Calyskan, U., Martini, S., & Heinritz, W. (2006). Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive). Journal of Pediatric Hematology Oncology, 28(3), 123–125.CrossRef
61.
Zurück zum Zitat Keren, B., Hadchouel, A., Saba, S., Sznajer, Y., Bonneau, D., Leheup, B., et al. (2004). PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience. Journal of Medical Genetics, 41(11), e117.PubMedCrossRef Keren, B., Hadchouel, A., Saba, S., Sznajer, Y., Bonneau, D., Leheup, B., et al. (2004). PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience. Journal of Medical Genetics, 41(11), e117.PubMedCrossRef
62.
Zurück zum Zitat Merks, J. H., Caron, H. N., & Hennekam, R. C. (2005). High incidence of malformation syndromes in a series of 1,073 children with cancer. American Journal of Medical Genetics, 134(2), 132–143.PubMed Merks, J. H., Caron, H. N., & Hennekam, R. C. (2005). High incidence of malformation syndromes in a series of 1,073 children with cancer. American Journal of Medical Genetics, 134(2), 132–143.PubMed
63.
Zurück zum Zitat Xu, R., Yu, Y., Zheng, S., Zhao, X., Dong, Q., He, Z., et al. (2005). Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia. Blood, 106(9), 3142–3149.PubMedCrossRef Xu, R., Yu, Y., Zheng, S., Zhao, X., Dong, Q., He, Z., et al. (2005). Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia. Blood, 106(9), 3142–3149.PubMedCrossRef
64.
Zurück zum Zitat Chan, R. J., Leedy, M. B., Munugalavadla, V., Voorhorst, C. S., Li, Y., Yu, M., et al. (2005). Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulating factor. Blood, 105(9), 3737–3742.PubMedCrossRef Chan, R. J., Leedy, M. B., Munugalavadla, V., Voorhorst, C. S., Li, Y., Yu, M., et al. (2005). Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulating factor. Blood, 105(9), 3737–3742.PubMedCrossRef
65.
Zurück zum Zitat Mohi, M. G., Williams, I. R., Dearolf, C. R., Chan, G., Kutok, J. L., Cohen, S., et al. (2005). Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell, 7(2), 179–191.PubMedCrossRef Mohi, M. G., Williams, I. R., Dearolf, C. R., Chan, G., Kutok, J. L., Cohen, S., et al. (2005). Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell, 7(2), 179–191.PubMedCrossRef
66.
Zurück zum Zitat Yu, W. M., Daino, H., Chen, J., Bunting, K. D., & Qu, C. K. (2006). Effects of a leukemia-associated gain-of-function mutation of SHP-2 phosphatase on interleukin-3 signaling. Journal of Biological Chemistry, 281(9), 5426–5434.PubMedCrossRef Yu, W. M., Daino, H., Chen, J., Bunting, K. D., & Qu, C. K. (2006). Effects of a leukemia-associated gain-of-function mutation of SHP-2 phosphatase on interleukin-3 signaling. Journal of Biological Chemistry, 281(9), 5426–5434.PubMedCrossRef
67.
Zurück zum Zitat Emanuel, P. D., Shannon, K. M., & Castleberry, R. P. (1996). Juvenile myelomonocytic leukemia: molecular understanding and prospects for therapy. Molecular Medicine Today, 2(11), 468–475.PubMedCrossRef Emanuel, P. D., Shannon, K. M., & Castleberry, R. P. (1996). Juvenile myelomonocytic leukemia: molecular understanding and prospects for therapy. Molecular Medicine Today, 2(11), 468–475.PubMedCrossRef
68.
Zurück zum Zitat Schubbert, S., Shannon, K., & Bollag, G. (2007). Hyperactive Ras in developmental disorders and cancer. Nature Reviews. Cancer, 7(4), 295–308.PubMedCrossRef Schubbert, S., Shannon, K., & Bollag, G. (2007). Hyperactive Ras in developmental disorders and cancer. Nature Reviews. Cancer, 7(4), 295–308.PubMedCrossRef
69.
Zurück zum Zitat Kratz, C. P., Niemeyer, C. M., Thomas, C., Bauhuber, S., Matejas, V., Bergstrasser, E., et al. (2007). Mutation analysis of Son of Sevenless in juvenile myelomonocytic leukemia. Leukemia, 21(5), 1108–1109.PubMed Kratz, C. P., Niemeyer, C. M., Thomas, C., Bauhuber, S., Matejas, V., Bergstrasser, E., et al. (2007). Mutation analysis of Son of Sevenless in juvenile myelomonocytic leukemia. Leukemia, 21(5), 1108–1109.PubMed
70.
Zurück zum Zitat Schubbert, S., Lieuw, K., Rowe, S. L., Lee, C. M., Li, X., Loh, M. L., et al. (2005). Functional analysis of leukemia-associated PTPN11 mutations in primary hematopoietic cells. Blood, 106(1), 311–317.PubMedCrossRef Schubbert, S., Lieuw, K., Rowe, S. L., Lee, C. M., Li, X., Loh, M. L., et al. (2005). Functional analysis of leukemia-associated PTPN11 mutations in primary hematopoietic cells. Blood, 106(1), 311–317.PubMedCrossRef
71.
Zurück zum Zitat Zhang, Y. Y., Vik, T. A., Ryder, J. W., Srour, E. F., Jacks, T., Shannon, K., et al. (1998). Nf1 regulates hematopoietic progenitor cell growth and ras signaling in response to multiple cytokines. Journal of Experimental Medicine, 187(11), 1893–1902.PubMedCrossRef Zhang, Y. Y., Vik, T. A., Ryder, J. W., Srour, E. F., Jacks, T., Shannon, K., et al. (1998). Nf1 regulates hematopoietic progenitor cell growth and ras signaling in response to multiple cytokines. Journal of Experimental Medicine, 187(11), 1893–1902.PubMedCrossRef
72.
Zurück zum Zitat Le, D. T., Kong, N., Zhu, Y., Lauchle, J. O., Aiyigari, A., Braun, B. S., et al. (2004). Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder. Blood, 103(11), 4243–4250.PubMedCrossRef Le, D. T., Kong, N., Zhu, Y., Lauchle, J. O., Aiyigari, A., Braun, B. S., et al. (2004). Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder. Blood, 103(11), 4243–4250.PubMedCrossRef
73.
Zurück zum Zitat Donovan, S., See, W., Bonifas, J., Stokoe, D., & Shannon, K. M. (2002). Hyperactivation of protein kinase B and ERK have discrete effects on survival, proliferation, and cytokine expression in Nf1-deficient myeloid cells. Cancer Cell, 2(6), 507–514.PubMedCrossRef Donovan, S., See, W., Bonifas, J., Stokoe, D., & Shannon, K. M. (2002). Hyperactivation of protein kinase B and ERK have discrete effects on survival, proliferation, and cytokine expression in Nf1-deficient myeloid cells. Cancer Cell, 2(6), 507–514.PubMedCrossRef
74.
Zurück zum Zitat Largaespada, D. A., Brannan, C. I., Jenkins, N. A., & Copeland, N. G. (1996). Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nature Genetics, 12(2), 137–143.PubMedCrossRef Largaespada, D. A., Brannan, C. I., Jenkins, N. A., & Copeland, N. G. (1996). Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nature Genetics, 12(2), 137–143.PubMedCrossRef
75.
Zurück zum Zitat Bollag, G., Clapp, D. W., Shih, S., Adler, F., Zhang, Y. Y., Thompson, P., et al. (1996). Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nature Genetics, 12(2), 144–148.PubMedCrossRef Bollag, G., Clapp, D. W., Shih, S., Adler, F., Zhang, Y. Y., Thompson, P., et al. (1996). Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nature Genetics, 12(2), 144–148.PubMedCrossRef
76.
Zurück zum Zitat Braun, B. S., Tuveson, D. A., Kong, N., Le, D. T., Kogan, S. C., Rozmus, J., et al. (2004). Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proceedings of the National Academy of Sciences of the United States of America, 101(2), 597–602.PubMedCrossRef Braun, B. S., Tuveson, D. A., Kong, N., Le, D. T., Kogan, S. C., Rozmus, J., et al. (2004). Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proceedings of the National Academy of Sciences of the United States of America, 101(2), 597–602.PubMedCrossRef
77.
Zurück zum Zitat Chan, I. T., Kutok, J. L., Williams, I. R., Cohen, S., Kelly, L., Shigematsu, H., et al. (2004). Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. Journal of Clinical Investigation, 113(4), 528–538.PubMed Chan, I. T., Kutok, J. L., Williams, I. R., Cohen, S., Kelly, L., Shigematsu, H., et al. (2004). Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. Journal of Clinical Investigation, 113(4), 528–538.PubMed
78.
Zurück zum Zitat Li, S., Gillessen, S., Tomasson, M. H., Dranoff, G., Gilliland, D. G., & Van Etten, R. A. (2001). Interleukin 3 and granulocyte-macrophage colony-stimulating factor are not required for induction of chronic myeloid leukemia-like myeloproliferative disease in mice by BCR/ABL. Blood, 97(5), 1442–1450.PubMedCrossRef Li, S., Gillessen, S., Tomasson, M. H., Dranoff, G., Gilliland, D. G., & Van Etten, R. A. (2001). Interleukin 3 and granulocyte-macrophage colony-stimulating factor are not required for induction of chronic myeloid leukemia-like myeloproliferative disease in mice by BCR/ABL. Blood, 97(5), 1442–1450.PubMedCrossRef
79.
Zurück zum Zitat Zhang, Y., Taylor, B. R., Shannon, K., & Clapp, D. W. (2001). Quantitative effects of Nf1 inactivation on in vivo hematopoiesis. Journal of Clinical Investigation, 108(5), 709–715.PubMed Zhang, Y., Taylor, B. R., Shannon, K., & Clapp, D. W. (2001). Quantitative effects of Nf1 inactivation on in vivo hematopoiesis. Journal of Clinical Investigation, 108(5), 709–715.PubMed
80.
Zurück zum Zitat Chen, Y., Wen, R., Yang, S., Schuman, J., Zhang, E. E., Yi, T., et al. (2003). Identification of Shp-2 as a Stat5A phosphatase. Journal of Biological Chemistry, 278(19), 16520–16527.PubMedCrossRef Chen, Y., Wen, R., Yang, S., Schuman, J., Zhang, E. E., Yi, T., et al. (2003). Identification of Shp-2 as a Stat5A phosphatase. Journal of Biological Chemistry, 278(19), 16520–16527.PubMedCrossRef
81.
Zurück zum Zitat Huang, W., Saberwal, G., Horvath, E., Zhu, C., Lindsey, S., & Eklund, E. A. (2006). Leukemia-associated, constitutively active mutants of SHP2 protein tyrosine phosphatase inhibit NF1 transcriptional activation by the interferon consensus sequence binding protein. Molecular and Cellular Biology, 26(17), 6311–6332.PubMedCrossRef Huang, W., Saberwal, G., Horvath, E., Zhu, C., Lindsey, S., & Eklund, E. A. (2006). Leukemia-associated, constitutively active mutants of SHP2 protein tyrosine phosphatase inhibit NF1 transcriptional activation by the interferon consensus sequence binding protein. Molecular and Cellular Biology, 26(17), 6311–6332.PubMedCrossRef
82.
Zurück zum Zitat Holtschke, T., Lohler, J., Kanno, Y., Fehr, T., Giese, N., Rosenbauer, F., et al. (1996). Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell, 87(2), 307–317.PubMedCrossRef Holtschke, T., Lohler, J., Kanno, Y., Fehr, T., Giese, N., Rosenbauer, F., et al. (1996). Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell, 87(2), 307–317.PubMedCrossRef
83.
Zurück zum Zitat Kautz, B., Kakar, R., David, E., & Eklund, E. A. (2001). SHP1 protein-tyrosine phosphatase inhibits gp91PHOX and p67PHOX expression by inhibiting interaction of PU.1, IRF1, interferon consensus sequence-binding protein, and CREB-binding protein with homologous Cis elements in the CYBB and NCF2 genes. Journal of Biological Chemistry, 276(41), 37868–37878.PubMed Kautz, B., Kakar, R., David, E., & Eklund, E. A. (2001). SHP1 protein-tyrosine phosphatase inhibits gp91PHOX and p67PHOX expression by inhibiting interaction of PU.1, IRF1, interferon consensus sequence-binding protein, and CREB-binding protein with homologous Cis elements in the CYBB and NCF2 genes. Journal of Biological Chemistry, 276(41), 37868–37878.PubMed
84.
Zurück zum Zitat Lindsey, S., Huang, W., Wang, H., Horvath, E., Zhu, C., & Eklund, E. A. (2007). Activation of SHP2 protein-tyrosine phosphatase increases HoxA10-induced repression of the genes encoding gp91(PHOX) and p67(PHOX). Journal of Biological Chemistry, 282(4), 2237–2249.PubMedCrossRef Lindsey, S., Huang, W., Wang, H., Horvath, E., Zhu, C., & Eklund, E. A. (2007). Activation of SHP2 protein-tyrosine phosphatase increases HoxA10-induced repression of the genes encoding gp91(PHOX) and p67(PHOX). Journal of Biological Chemistry, 282(4), 2237–2249.PubMedCrossRef
85.
Zurück zum Zitat Mason, J. M., Morrison, D. J., Basson, M. A., & Licht, J. D. (2006). Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signaling. Trends in Cell Biology, 16(1), 45–54.PubMedCrossRef Mason, J. M., Morrison, D. J., Basson, M. A., & Licht, J. D. (2006). Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signaling. Trends in Cell Biology, 16(1), 45–54.PubMedCrossRef
86.
Zurück zum Zitat Basson, M. A., Akbulut, S., Watson-Johnson, J., Simon, R., Carroll, T. J., Shakya, R., et al. (2005). Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Developmental Cell, 8(2), 229–239.PubMedCrossRef Basson, M. A., Akbulut, S., Watson-Johnson, J., Simon, R., Carroll, T. J., Shakya, R., et al. (2005). Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Developmental Cell, 8(2), 229–239.PubMedCrossRef
87.
Zurück zum Zitat Taketomi, T., Yoshiga, D., Taniguchi, K., Kobayashi, T., Nonami, A., Kato, R., et al. (2005). Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia. Nature Neuroscience, 8(7), 855–857.PubMed Taketomi, T., Yoshiga, D., Taniguchi, K., Kobayashi, T., Nonami, A., Kato, R., et al. (2005). Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia. Nature Neuroscience, 8(7), 855–857.PubMed
88.
Zurück zum Zitat Shim, K., Minowada, G., Coling, D. E., & Martin, G. R. (2005). Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling. Developmental Cell, 8(4), 553–564.PubMedCrossRef Shim, K., Minowada, G., Coling, D. E., & Martin, G. R. (2005). Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling. Developmental Cell, 8(4), 553–564.PubMedCrossRef
89.
Zurück zum Zitat Klein, O. D., Minowada, G., Peterkova, R., Kangas, A., Yu, B. D., Lesot, H., et al. (2006). Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling. Developmental Cell, 11(2), 181–190.PubMedCrossRef Klein, O. D., Minowada, G., Peterkova, R., Kangas, A., Yu, B. D., Lesot, H., et al. (2006). Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling. Developmental Cell, 11(2), 181–190.PubMedCrossRef
90.
Zurück zum Zitat Taniguchi, K., Ayada, T., Ichiyama, K., Kohno, R., Yonemitsu, Y., Minami, Y., et al. (2007). Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling. Biochemical and Biophysical Research Communications, 352(4), 896–902.PubMedCrossRef Taniguchi, K., Ayada, T., Ichiyama, K., Kohno, R., Yonemitsu, Y., Minami, Y., et al. (2007). Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling. Biochemical and Biophysical Research Communications, 352(4), 896–902.PubMedCrossRef
91.
Zurück zum Zitat Wakioka, T., Sasaki, A., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., et al. (2001). Spred is a Sprouty-related suppressor of Ras signalling. Nature, 412(6847), 647–651.PubMedCrossRef Wakioka, T., Sasaki, A., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., et al. (2001). Spred is a Sprouty-related suppressor of Ras signalling. Nature, 412(6847), 647–651.PubMedCrossRef
92.
Zurück zum Zitat Kato, R., Nonami, A., Taketomi, T., Wakioka, T., Kuroiwa, A., Matsuda, Y., et al. (2003). Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation. Biochemical and Biophysical Research Communications, 302(4), 767–772.PubMedCrossRef Kato, R., Nonami, A., Taketomi, T., Wakioka, T., Kuroiwa, A., Matsuda, Y., et al. (2003). Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation. Biochemical and Biophysical Research Communications, 302(4), 767–772.PubMedCrossRef
93.
Zurück zum Zitat Nonami, A., Kato, R., Taniguchi, K., Yoshiga, D., Taketomi, T., Fukuyama, S., et al. (2004). Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells. Journal of Biological Chemistry, 279(50), 52543–52551.PubMedCrossRef Nonami, A., Kato, R., Taniguchi, K., Yoshiga, D., Taketomi, T., Fukuyama, S., et al. (2004). Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells. Journal of Biological Chemistry, 279(50), 52543–52551.PubMedCrossRef
94.
Zurück zum Zitat Taniguchi, K., Kohno, R., Ayada, T., Kato, R., Ichiyama, K., Morisada, T., et al. (2007). Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling. Molecular and Cellular Biology, 27(12), 4541–4550.PubMedCrossRef Taniguchi, K., Kohno, R., Ayada, T., Kato, R., Ichiyama, K., Morisada, T., et al. (2007). Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling. Molecular and Cellular Biology, 27(12), 4541–4550.PubMedCrossRef
95.
Zurück zum Zitat Inoue, H., Kato, R., Fukuyama, S., Nonami, A., Taniguchi, K., Matsumoto, K., et al. (2005). Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness. Journal of Experimental Medicine, 201(1), 73–82.PubMedCrossRef Inoue, H., Kato, R., Fukuyama, S., Nonami, A., Taniguchi, K., Matsumoto, K., et al. (2005). Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness. Journal of Experimental Medicine, 201(1), 73–82.PubMedCrossRef
96.
Zurück zum Zitat Bundschu, K., Knobeloch, K. P., Ullrich, M., Schinke, T., Amling, M., Engelhardt, C. M., et al. (2005). Gene disruption of Spred-2 causes dwarfism. Journal of Biological Chemistry, 280(31), 28572–28580.PubMedCrossRef Bundschu, K., Knobeloch, K. P., Ullrich, M., Schinke, T., Amling, M., Engelhardt, C. M., et al. (2005). Gene disruption of Spred-2 causes dwarfism. Journal of Biological Chemistry, 280(31), 28572–28580.PubMedCrossRef
97.
Zurück zum Zitat Nobuhisa, I., Kato, R., Inoue, H., Takizawa, M., Okita, K., Yoshimura, A., et al. (2004). Spred-2 suppresses aorta-gonad-mesonephros hematopoiesis by inhibiting MAP kinase activation. Journal of Experimental Medicine, 199(5), 737–742.PubMedCrossRef Nobuhisa, I., Kato, R., Inoue, H., Takizawa, M., Okita, K., Yoshimura, A., et al. (2004). Spred-2 suppresses aorta-gonad-mesonephros hematopoiesis by inhibiting MAP kinase activation. Journal of Experimental Medicine, 199(5), 737–742.PubMedCrossRef
98.
Zurück zum Zitat Irish, J. M., Hovland, R., Krutzik, P. O., Perez, O. D., Bruserud, O., Gjertsen, B. T., et al. (2004). Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell, 118(2), 217–228.PubMedCrossRef Irish, J. M., Hovland, R., Krutzik, P. O., Perez, O. D., Bruserud, O., Gjertsen, B. T., et al. (2004). Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell, 118(2), 217–228.PubMedCrossRef
99.
Zurück zum Zitat Ornatsky, O., Baranov, V. I., Bandura, D. R., Tanner, S. D., & Dick, J. (2006). Multiple cellular antigen detection by ICP-MS. Journal of Immunological Methods, 308(1–2), 68–76.PubMedCrossRef Ornatsky, O., Baranov, V. I., Bandura, D. R., Tanner, S. D., & Dick, J. (2006). Multiple cellular antigen detection by ICP-MS. Journal of Immunological Methods, 308(1–2), 68–76.PubMedCrossRef
100.
Zurück zum Zitat Loh, M. L., Martinelli, S., Cordeddu, V., Reynolds, M. G., Vattikuti, S., Lee, C. M., et al. (2005). Acquired PTPN11 mutations occur rarely in adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leukemia Research, 29(4), 459–462.PubMedCrossRef Loh, M. L., Martinelli, S., Cordeddu, V., Reynolds, M. G., Vattikuti, S., Lee, C. M., et al. (2005). Acquired PTPN11 mutations occur rarely in adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leukemia Research, 29(4), 459–462.PubMedCrossRef
101.
Zurück zum Zitat Ren, R. (2005). Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nature Reviews. Cancer, 5(3), 172–183.PubMedCrossRef Ren, R. (2005). Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nature Reviews. Cancer, 5(3), 172–183.PubMedCrossRef
102.
Zurück zum Zitat O’Hare, T., Corbin, A. S., & Druker, B. J. (2006). Targeted CML therapy: controlling drug resistance, seeking cure. Current Opinion in Genetics & Development, 16(1), 92–99.CrossRef O’Hare, T., Corbin, A. S., & Druker, B. J. (2006). Targeted CML therapy: controlling drug resistance, seeking cure. Current Opinion in Genetics & Development, 16(1), 92–99.CrossRef
103.
Zurück zum Zitat Million, R. P., & Van Etten, R. A. (2000). The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase. Blood, 96(2), 664–670.PubMed Million, R. P., & Van Etten, R. A. (2000). The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase. Blood, 96(2), 664–670.PubMed
104.
Zurück zum Zitat Zhang, X., Subrahmanyam, R., Wong, R., Gross, A. W., & Ren, R. (2001). The NH(2)-terminal coiled-coil domain and tyrosine 177 play important roles in induction of a myeloproliferative disease in mice by Bcr-Abl. Molecular and Cellular Biology, 21(3), 840–853.PubMedCrossRef Zhang, X., Subrahmanyam, R., Wong, R., Gross, A. W., & Ren, R. (2001). The NH(2)-terminal coiled-coil domain and tyrosine 177 play important roles in induction of a myeloproliferative disease in mice by Bcr-Abl. Molecular and Cellular Biology, 21(3), 840–853.PubMedCrossRef
105.
Zurück zum Zitat He, Y., Wertheim, J. A., Xu, L., Miller, J. P., Karnell, F. G., Choi, J. K., et al. (2002). The coiled-coil domain and Tyr177 of bcr are required to induce a murine chronic myelogenous leukemia-like disease by bcr/abl. Blood, 99(8), 2957–2968.PubMedCrossRef He, Y., Wertheim, J. A., Xu, L., Miller, J. P., Karnell, F. G., Choi, J. K., et al. (2002). The coiled-coil domain and Tyr177 of bcr are required to induce a murine chronic myelogenous leukemia-like disease by bcr/abl. Blood, 99(8), 2957–2968.PubMedCrossRef
106.
Zurück zum Zitat Sattler, M., & Griffin, J. D. (2001). Mechanisms of transformation by the BCR/ABL oncogene. International Journal of Hematology, 73(3), 278–291.PubMedCrossRef Sattler, M., & Griffin, J. D. (2001). Mechanisms of transformation by the BCR/ABL oncogene. International Journal of Hematology, 73(3), 278–291.PubMedCrossRef
107.
Zurück zum Zitat Sattler, M., Mohi, M. G., Pride, Y. B., Quinnan, L. R., Malouf, N. A., Podar, K., et al. (2002). Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell, 1(5), 479–492.PubMedCrossRef Sattler, M., Mohi, M. G., Pride, Y. B., Quinnan, L. R., Malouf, N. A., Podar, K., et al. (2002). Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell, 1(5), 479–492.PubMedCrossRef
108.
Zurück zum Zitat Scherr, M., Chaturvedi, A., Battmer, K., Dallmann, I., Schultheis, B., Ganser, A., et al. (2006). Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML). Blood, 107(8), 3279–3287.PubMedCrossRef Scherr, M., Chaturvedi, A., Battmer, K., Dallmann, I., Schultheis, B., Ganser, A., et al. (2006). Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML). Blood, 107(8), 3279–3287.PubMedCrossRef
109.
Zurück zum Zitat Chen, J., Yu, W. M., Daino, H., Broxmeyer, H. E., Druker, B. J., & Qu, C. K. (2007). SHP-2 phosphatase is required for hematopoietic cell transformation by Bcr-Abl. Blood, 109(2), 778–785.PubMedCrossRef Chen, J., Yu, W. M., Daino, H., Broxmeyer, H. E., Druker, B. J., & Qu, C. K. (2007). SHP-2 phosphatase is required for hematopoietic cell transformation by Bcr-Abl. Blood, 109(2), 778–785.PubMedCrossRef
110.
Zurück zum Zitat Teal, H. E., Ni, S., Xu, J., Finkelstein, L. D., Cheng, A. M., Paulson, R. F., et al. (2006). GRB2-mediated recruitment of GAB2, but not GAB1, to SF-STK supports the expansion of Friend virus-infected erythroid progenitor cells. Oncogene, 25(17), 2433–2443.PubMedCrossRef Teal, H. E., Ni, S., Xu, J., Finkelstein, L. D., Cheng, A. M., Paulson, R. F., et al. (2006). GRB2-mediated recruitment of GAB2, but not GAB1, to SF-STK supports the expansion of Friend virus-infected erythroid progenitor cells. Oncogene, 25(17), 2433–2443.PubMedCrossRef
111.
Zurück zum Zitat Ischenko, I., Petrenko, O., Gu, H., & Hayman, M. J. (2003). Scaffolding protein Gab2 mediates fibroblast transformation by the SEA tyrosine kinase. Oncogene, 22(41), 6311–6318.PubMedCrossRef Ischenko, I., Petrenko, O., Gu, H., & Hayman, M. J. (2003). Scaffolding protein Gab2 mediates fibroblast transformation by the SEA tyrosine kinase. Oncogene, 22(41), 6311–6318.PubMedCrossRef
112.
Zurück zum Zitat Niimi, H., Harada, H., Harada, Y., Ding, Y., Imagawa, J., Inaba, T., et al. (2006). Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations. Leukemia, 20(4), 635–644.PubMedCrossRef Niimi, H., Harada, H., Harada, Y., Ding, Y., Imagawa, J., Inaba, T., et al. (2006). Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations. Leukemia, 20(4), 635–644.PubMedCrossRef
113.
Zurück zum Zitat Hou, H. A., Chou, W. C., Lin, L. I., Chen, C. Y., Tang, J. L., Tseng, M. H., et al. (2007). Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD. Leukemia, in press. Nov 1. Hou, H. A., Chou, W. C., Lin, L. I., Chen, C. Y., Tang, J. L., Tseng, M. H., et al. (2007). Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD. Leukemia, in press. Nov 1.
114.
Zurück zum Zitat Yamada, K., Nishida, K., Hibi, M., Hirano, T., & Matsuda, Y. (2001). Comparative FISH mapping of Gab1 and Gab2 genes in human, mouse and rat. Cytogenetics and Cell Genetics, 94(1–2), 39–42.PubMed Yamada, K., Nishida, K., Hibi, M., Hirano, T., & Matsuda, Y. (2001). Comparative FISH mapping of Gab1 and Gab2 genes in human, mouse and rat. Cytogenetics and Cell Genetics, 94(1–2), 39–42.PubMed
115.
Zurück zum Zitat Bekri, S., Adelaide, J., Merscher, S., Grosgeorge, J., Caroli-Bosc, F., Perucca-Lostanlen, D., et al. (1997). Detailed map of a region commonly amplified at 11q13–>q14 in human breast carcinoma. Cytogenetics and Cell Genetics, 79(1–2), 125–131.PubMed Bekri, S., Adelaide, J., Merscher, S., Grosgeorge, J., Caroli-Bosc, F., Perucca-Lostanlen, D., et al. (1997). Detailed map of a region commonly amplified at 11q13–>q14 in human breast carcinoma. Cytogenetics and Cell Genetics, 79(1–2), 125–131.PubMed
116.
Zurück zum Zitat Ormandy, C. J., Musgrove, E. A., Hui, R., Daly, R. J., & Sutherland, R. L. (2003). Cyclin D1, EMS1 and 11q13 amplification in breast cancer. Breast Cancer Research and Treatment, 78(3), 323–335.PubMedCrossRef Ormandy, C. J., Musgrove, E. A., Hui, R., Daly, R. J., & Sutherland, R. L. (2003). Cyclin D1, EMS1 and 11q13 amplification in breast cancer. Breast Cancer Research and Treatment, 78(3), 323–335.PubMedCrossRef
117.
Zurück zum Zitat Brummer, T., Schramek, D., Hayes, V. M., Bennett, H. L., Caldon, C. E., Musgrove, E. A., et al. (2006). Increased proliferation and altered growth factor dependence of human mammary epithelial cells overexpressing the Gab2 docking protein. Journal of Biological Chemistry, 281(1), 626–637.PubMedCrossRef Brummer, T., Schramek, D., Hayes, V. M., Bennett, H. L., Caldon, C. E., Musgrove, E. A., et al. (2006). Increased proliferation and altered growth factor dependence of human mammary epithelial cells overexpressing the Gab2 docking protein. Journal of Biological Chemistry, 281(1), 626–637.PubMedCrossRef
118.
Zurück zum Zitat Bentires-Alj, M., Gil, S. G., Chan, R., Wang, Z. C., Wang, Y., Imanaka, N., et al. (2006). A role for the scaffolding adapter GAB2 in breast cancer. Nature Medicine, 12(1), 114–121.PubMedCrossRef Bentires-Alj, M., Gil, S. G., Chan, R., Wang, Z. C., Wang, Y., Imanaka, N., et al. (2006). A role for the scaffolding adapter GAB2 in breast cancer. Nature Medicine, 12(1), 114–121.PubMedCrossRef
119.
Zurück zum Zitat Ke, Y., Wu, D., Princen, F., Nguyen, T., Pang, Y., Lesperance, J., et al. (2007). Role of Gab2 in mammary tumorigenesis and metastasis. Oncogene, 26(34), 4951–4960.PubMedCrossRef Ke, Y., Wu, D., Princen, F., Nguyen, T., Pang, Y., Lesperance, J., et al. (2007). Role of Gab2 in mammary tumorigenesis and metastasis. Oncogene, 26(34), 4951–4960.PubMedCrossRef
120.
Zurück zum Zitat Hatakeyama, M. (2004). Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nature Reviews. Cancer, 4(9), 688–694.PubMedCrossRef Hatakeyama, M. (2004). Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nature Reviews. Cancer, 4(9), 688–694.PubMedCrossRef
121.
Zurück zum Zitat Higashi, H., Tsutsumi, R., Muto, S., Sugiyama, T., Azuma, T., Asaka, M., et al. (2002). SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science, 295(5555), 683–686.PubMedCrossRef Higashi, H., Tsutsumi, R., Muto, S., Sugiyama, T., Azuma, T., Asaka, M., et al. (2002). SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science, 295(5555), 683–686.PubMedCrossRef
122.
Zurück zum Zitat Tsutsumi, R., Higashi, H., Higuchi, M., Okada, M., & Hatakeyama, M. (2003). Attenuation of Helicobacter pylori CagA x SHP-2 signaling by interaction between CagA and C-terminal Src kinase. Journal of Biological Chemistry, 278(6), 3664–3670.PubMedCrossRef Tsutsumi, R., Higashi, H., Higuchi, M., Okada, M., & Hatakeyama, M. (2003). Attenuation of Helicobacter pylori CagA x SHP-2 signaling by interaction between CagA and C-terminal Src kinase. Journal of Biological Chemistry, 278(6), 3664–3670.PubMedCrossRef
123.
Zurück zum Zitat Higuchi, M., Tsutsumi, R., Higashi, H., & Hatakeyama, M. (2004). Conditional gene silencing utilizing the lac repressor reveals a role of SHP-2 in cagA-positive Helicobacter pylori pathogenicity. Cancer Science, 95(5), 442–447.PubMedCrossRef Higuchi, M., Tsutsumi, R., Higashi, H., & Hatakeyama, M. (2004). Conditional gene silencing utilizing the lac repressor reveals a role of SHP-2 in cagA-positive Helicobacter pylori pathogenicity. Cancer Science, 95(5), 442–447.PubMedCrossRef
124.
Zurück zum Zitat Tsutsumi, R., Takahashi, A., Azuma, T., Higashi, H., & Hatakeyama, M. (2006). Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA. Molecular and Cellular Biology, 26(1), 261–276.PubMedCrossRef Tsutsumi, R., Takahashi, A., Azuma, T., Higashi, H., & Hatakeyama, M. (2006). Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA. Molecular and Cellular Biology, 26(1), 261–276.PubMedCrossRef
125.
Zurück zum Zitat Manes, S., Mira, E., Gomez-Mouton, C., Zhao, Z. J., Lacalle, R. A., & Martinez, A. C. (1999). Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility. Molecular and Cellular Biology, 19(4), 3125–3135.PubMed Manes, S., Mira, E., Gomez-Mouton, C., Zhao, Z. J., Lacalle, R. A., & Martinez, A. C. (1999). Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility. Molecular and Cellular Biology, 19(4), 3125–3135.PubMed
126.
Zurück zum Zitat Vadlamudi, R. K., Adam, L., Nguyen, D., Santos, M., & Kumar, R. (2002). Differential regulation of components of the focal adhesion complex by heregulin: role of phosphatase SHP-2. Journal of Cellular Physiology, 190(2), 189–199.PubMedCrossRef Vadlamudi, R. K., Adam, L., Nguyen, D., Santos, M., & Kumar, R. (2002). Differential regulation of components of the focal adhesion complex by heregulin: role of phosphatase SHP-2. Journal of Cellular Physiology, 190(2), 189–199.PubMedCrossRef
127.
Zurück zum Zitat Oh, E. S., Gu, H., Saxton, T. M., Timms, J. F., Hausdorff, S., Frevert, E. U., et al. (1999). Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2. Molecular and Cellular Biology, 19(4), 3205–3215.PubMed Oh, E. S., Gu, H., Saxton, T. M., Timms, J. F., Hausdorff, S., Frevert, E. U., et al. (1999). Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2. Molecular and Cellular Biology, 19(4), 3205–3215.PubMed
128.
Zurück zum Zitat Yu, D. H., Qu, C. K., Henegariu, O., Lu, X., & Feng, G. S. (1998). Protein-tyrosine phosphatase Shp-2 regulates cell spreading, migration, and focal adhesion. Journal of Biological Chemistry, 273(33), 21125–21131.PubMedCrossRef Yu, D. H., Qu, C. K., Henegariu, O., Lu, X., & Feng, G. S. (1998). Protein-tyrosine phosphatase Shp-2 regulates cell spreading, migration, and focal adhesion. Journal of Biological Chemistry, 273(33), 21125–21131.PubMedCrossRef
129.
Zurück zum Zitat Higashi, H., Nakaya, A., Tsutsumi, R., Yokoyama, K., Fujii, Y., Ishikawa, S., et al. (2004). Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation. Journal of Biological Chemistry, 279(17), 17205–17216.PubMedCrossRef Higashi, H., Nakaya, A., Tsutsumi, R., Yokoyama, K., Fujii, Y., Ishikawa, S., et al. (2004). Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation. Journal of Biological Chemistry, 279(17), 17205–17216.PubMedCrossRef
130.
Zurück zum Zitat Saadat, I., Higashi, H., Obuse, C., Umeda, M., Murata-Kamiya, N., Saito, Y., et al. (2007). Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature, 447(7142), 330–333.PubMedCrossRef Saadat, I., Higashi, H., Obuse, C., Umeda, M., Murata-Kamiya, N., Saito, Y., et al. (2007). Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature, 447(7142), 330–333.PubMedCrossRef
131.
Zurück zum Zitat Raabe, T., Riesgo-Escovar, J., Liu, X., Bausenwein, B. S., Deak, P., Maroy, P., et al. (1996). DOS, a novel pleckstrin homology domain-containing protein required for signal transduction between sevenless and Ras1 in Drosophila. Cell, 85(6), 911–920.PubMedCrossRef Raabe, T., Riesgo-Escovar, J., Liu, X., Bausenwein, B. S., Deak, P., Maroy, P., et al. (1996). DOS, a novel pleckstrin homology domain-containing protein required for signal transduction between sevenless and Ras1 in Drosophila. Cell, 85(6), 911–920.PubMedCrossRef
132.
Zurück zum Zitat Chauhan, D., Hideshima, T., Pandey, P., Treon, S., Teoh, G., Raje, N., et al. (1999). RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells. Oncogene, 18(48), 6733–6740.PubMedCrossRef Chauhan, D., Hideshima, T., Pandey, P., Treon, S., Teoh, G., Raje, N., et al. (1999). RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells. Oncogene, 18(48), 6733–6740.PubMedCrossRef
133.
Zurück zum Zitat Agazie, Y. M., Movilla, N., Ischenko, I., & Hayman, M. J. (2003). The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3. Oncogene, 22(44), 6909–6918.PubMedCrossRef Agazie, Y. M., Movilla, N., Ischenko, I., & Hayman, M. J. (2003). The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3. Oncogene, 22(44), 6909–6918.PubMedCrossRef
134.
Zurück zum Zitat Bergsagel, P. L., & Kuehl, W. M. (2005). Molecular pathogenesis and a consequent classification of multiple myeloma. Journal of Clinical Oncology, 23(26), 6333–6338.PubMedCrossRef Bergsagel, P. L., & Kuehl, W. M. (2005). Molecular pathogenesis and a consequent classification of multiple myeloma. Journal of Clinical Oncology, 23(26), 6333–6338.PubMedCrossRef
135.
Zurück zum Zitat Burks, J., & Agazie, Y. M. (2006). Modulation of alpha-catenin Tyr phosphorylation by SHP2 positively effects cell transformation induced by the constitutively active FGFR3. Oncogene, 25(54), 7166–7179.PubMedCrossRef Burks, J., & Agazie, Y. M. (2006). Modulation of alpha-catenin Tyr phosphorylation by SHP2 positively effects cell transformation induced by the constitutively active FGFR3. Oncogene, 25(54), 7166–7179.PubMedCrossRef
136.
Zurück zum Zitat Voena, C., Conte, C., Ambrogio, C., Boeri Erba, E., Boccalatte, F., Mohammed, S., et al. (2007). The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration. Cancer Research, 67(9), 4278–4286.PubMedCrossRef Voena, C., Conte, C., Ambrogio, C., Boeri Erba, E., Boccalatte, F., Mohammed, S., et al. (2007). The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration. Cancer Research, 67(9), 4278–4286.PubMedCrossRef
137.
Zurück zum Zitat Charest, A., Wilker, E. W., McLaughlin, M. E., Lane, K., Gowda, R., Coven, S., et al. (2006). ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice. Cancer Research, 66(15), 7473–7481.PubMedCrossRef Charest, A., Wilker, E. W., McLaughlin, M. E., Lane, K., Gowda, R., Coven, S., et al. (2006). ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice. Cancer Research, 66(15), 7473–7481.PubMedCrossRef
Metadaten
Titel
The tyrosine phosphatase Shp2 (PTPN11) in cancer
verfasst von
Gordon Chan
Demetrios Kalaitzidis
Benjamin G. Neel
Publikationsdatum
01.06.2008
Verlag
Springer US
Erschienen in
Cancer and Metastasis Reviews / Ausgabe 2/2008
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-008-9126-y

Weitere Artikel der Ausgabe 2/2008

Cancer and Metastasis Reviews 2/2008 Zur Ausgabe

PREFACE

Preface

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.