Abstract
A complex intracellular signaling network mediates the multiple biological activities of G-protein-coupled receptors (GPCRs). Among them, monomeric GTPases and a family of closely related proline-targeted serine–threonine kinases, collectively known as Mitogen-Activated Protein Kinases (MAPKs), appears to play central roles in orchestrating the proliferative responses to multiple mitogens that act on GPCRs. Upon GDP/GTP exchange, monomeric GTPases control the phosphorylation of conserved threonine and tyrosine residues in MAPKs by their immediate upstream kinases, increasing their enzymatic activity and inducing their translocation to the nucleus where they phosphorylate transcription factors, thereby regulating the expression of genes playing a key role in normal and aberrant cell growth. Recently, a number of GPCRs have been engineered to provide exclusive activation by synthetic drug-like compounds while becoming insensitive to endogenous ligands. These engineered receptors, named Receptors Activated Solely by Synthetic Ligands (RASSLs), promise better understanding of GPCRs signaling in vitro and in vivo, thus representing ideal tools to selectively modulate MAPK signaling routes controlling a wide range of biological functions, from proliferation to differentiation, migration, invasion, and cell survival or death by apoptosis.
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References
Hepler, J. R., and Gilman, A. G. (1992) G proteins, Trends Biochem Sci 17, 383–387.
Gutkind, J. S. (1998) Cell growth control by G protein-coupled receptors: from signal transduction to signal integration, Oncogene 17, 1331–1342.
Pierce, K. L., Premont, R. T., and Lefkowitz, R. J. (2002) Seven-transmembrane receptors, Nat Rev Mol Cell Biol 3, 639–650.
Gutkind, J. S. (1998) The pathways connecting G protein-coupled receptors to the nucleus through divergent mitogen-activated protein kinase cascades, J Biol Chem 273, 1839–1842.
Dorsam, R. T., and Gutkind, J. S. (2007) G-protein-coupled receptors and cancer, Nat Rev Cancer 7, 79–94.
Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S., and Roth, B. L. (2007) Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand, Proc Natl Acad Sci USA 104, 5163–5168.
Conklin, B. R., Hsiao, E. C., Claeysen, S., Dumuis, A., Srinivasan, S., Forsayeth, J. R., Guettier, J. M., Chang, W. C., Pei, Y., McCarthy, K. D., Nissenson, R. A., Wess, J., Bockaert, J., and Roth, B. L. (2008) Engineering GPCR signaling pathways with RASSLs, Nat Methods 5, 673–678.
Marinissen, M. J., Chiariello, M., Pallante, M., and Gutkind, J. S. (1999) A network of mitogen-activated protein kinases links G protein-coupled receptors to the c-jun promoter: a role for c-Jun NH2-terminal kinase, p38s, and extracellular signal-regulated kinase 5, Mol Cell Biol 19, 4289–4301.
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Chiariello, M., Vaqué, J.P., Crespo, P., Gutkind, J.S. (2010). Activation of Ras and Rho GTPases and MAP Kinases by G-Protein-Coupled Receptors. In: Seger, R. (eds) MAP Kinase Signaling Protocols. Methods in Molecular Biology, vol 661. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-795-2_8
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DOI: https://doi.org/10.1007/978-1-60761-795-2_8
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Publisher Name: Humana Press, Totowa, NJ
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