DIFFERENTIAL REGULATION OF PYK2 AND FOCAL ADHESION KINASE (FAK) - THEC-TERMINAL DOMAIN OF FAK CONFERS RESPONSE TO CELL-ADHESION

Pyk2 is a recently described cytoplasmic tyrosine kinase that is relat ed to focal adhesion kinase (FAK) and can be activated by a variety of stimuli that elevate intracellular calcium, in this report, we showed that Pyk2 and FAK tyrosine phosphorylation are regulated differential ly by integrin-mediated cell adhesion and soluble factors both in rat aortic smooth muscle cells, which express endogenous Pyk2 and FAK, and in transfected Chinese hamster ovary cells, We also found that Pyk2 i s diffusely present throughout the cytoplasm, while FAT( is localized in focal contacts as expected, suggesting that the different localizat ion may account for their differential regulation, By analyzing a chim eric protein contain N-terminal and kinase domains of Pyk2 and C-termi nal domain of FAK, we provided evidence that the distinctive C-termina l domains of Pyk2 and FAR were responsible for their differential regu lation by integrins and soluble stimuli as well as their subcellular l ocalization, Finally, we correlated FAR, Pyk2, and the chimeric protei n binding to talin, but not paxillin, with their regulation by integri ns and focal contact localization, These results demonstrate that the distinctive C-terminal domain of Pyk2 and FAK confer their differentia l regulation by different subcellular localization and association wit h the cytoskeletal protein talin.