title: Focal adhesion targeting of v-Crk is essential for FAK phosphorylation and cell migration in mouse embryo fibroblasts deficient src family kinases or p130CAS.
abstract: 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.
authors.affiliation: National Research Laboratory (NRL), Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Myeong Gu
authors.initials: MG
authors.lastname: Yeo
authors.forename: Bong Hwan
authors.initials: BH
authors.lastname: Sung
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Oh
authors.forename: Zee Yong
authors.initials: ZY
authors.lastname: Park
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Marcantonio
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
mesh_terms: 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