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.
Yeo
Myeong Gu
MG
National Research Laboratory (NRL), Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
Sung
Bong Hwan
BH
Oh
Hye Jin
HJ
Park
Zee Yong
ZY
Marcantonio
Eugene E
EE
Song
Woo Keun
WK
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D022001:Focal Adhesions / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008845:Microinjections; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry / Q000378:metabolism; D050736:Oncogene Protein v-crk / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism