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Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain

Abstract

Etk/BMX, a member of the Btk family of tyrosine kinases, is highly expressed in cells with great migratory potential, including endothelial cells and metastatic carcinoma cell lines. Here, we present evidence that Etk is involved in integrin signalling and promotes cell migration. The activation of Etk by extracellular matrix proteins is regulated by FAK through an interaction between the PH domain of Etk and the FERM domain of FAK. The lack of Etk activation by extracellular matrix in FAK-null cells could be restored by co-transfection with wild-type FAK. Disrupting the interaction between Etk and FAK diminished the cell migration promoted by either kinase. Furthermore, inhibiting Etk expression in metastatic carcinoma cell lines with an antisense oligonucleotide blocks integrin-mediated migration of these cells. Taken together, our data indicate the essential role of the interaction of the PH domain of Etk and the FERM domain of FAK in integrin signalling.

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Figure 1: Regulation of Etk by integrins.
Figure 2: PH domain of Etk and FERM domain of FAK are involved in interaction between Etk and FAK.
Figure 3: Activation of Etk by FAK.
Figure 4: Etk is essential for integrin-mediated cell migration.

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Acknowledgements

We thank L. Higgins for mass spectrometry data analysis, J. McCarthy and J. Iida for providing reagents and advice throughout the study, D. Ilic and C. Damsky for providing FAK-null cells, and D. Schlaepfer, J. DeLarco and X. Zhang for helpful discussion. This work was supported by grants from Minnesota Medical Foundation, AHA (9960296Z) and NIH (CA85380) to Y.Q.

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Correspondence to Yun Qiu.

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Chen, R., Kim, O., Li, M. et al. Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain. Nat Cell Biol 3, 439–444 (2001). https://doi.org/10.1038/35074500

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