Focal adhesion targeting of v-Crk is essential for FAK phosphorylation and cell migration in mouse embryo fibroblasts deficient src family kinases or p130CAS

We examined the consequences of v‐Crk expression in mouse embryo fibroblasts deficient Src family kinases or p130CAS. We found that Src kinases are essential for p130CAS/v‐Crk signaling leading to FAK phosphorylation and cell migration in which Src is likely to mediate the focal adhesion targeting of v‐Crk. SYF cells showed only low levels of FAK phosphorylation and cell migration, even in the presence of v‐Crk. Expression of v‐Crk restored migration of p130CAS‐deficient cells to the level of wild‐type cells, most likely through the targeting of v‐Crk to focal adhesions by cSrc. In addition, we identified a new v‐Crk‐interacting protein that mediates v‐Crk signaling in p130CAS‐deficient cells. Using RT‐PCR and caspase cleavage assays, we confirmed that this protein is not p130CAS and is responsible for maintaining v‐Crk/Src signaling and migration in these. These findings suggest that focal adhesion targeting of v‐Crk is essential in v‐Crk‐mediated cellular signaling and that v‐Crk must form a complex with p130CAS or a p130CAS substitute to transduce signaling from the extracellular matrix. J. Cell. Physiol. 214: 604–613, 2008. © 2007 Wiley‐Liss, Inc.