Src kinase plays an essential role in integrin-mediated tyrosine phosphorylation of Crk-associated substrate p130Cas.
A novel signaling molecule p130Cas has been shown to undergo tyrosine phosphorylation in response to integrin-mediated cell adhesion. In this study, we have attempted to identify kinases that mediate Cas phosphorylation in integrin signaling by examining various mutant cell lines that do not express either p125FAK, c-Scr, c-Fyn or c-Abl. We found that deficiency of c-Src but not of other kinases completely abrogated integrin-mediated Cas phosphorylation. Importantly, paxillin phosphorylation was not compromised in each mutant cell line examined. These results suggest that c-Src primarily mediates adhesion-dependent Cas phosphorylation. As for paxillin phosphorylation, there may exist substantial redundancy amongst multiple kinases. Finally, adhesion-induced Cas phosphorylation resulted in its association with c-Crk adapter protein via the Crk-SH2 domain. Thus, Cas plays a role in the transmission of integrin-initiated signals through tyrosine phosphorylation and subsequent binding to c-Crk.
Hamasaki
K
K
Third Department of Internal Medicine, University of Tokyo, Japan.
Mimura
T
T
Morino
N
N
Furuya
H
H
Nakamoto
T
T
Aizawa
S
S
Morimoto
C
C
Yazaki
Y
Y
Hirai
H
H
Nojima
Y
Y
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D050719:Crk-Associated Substrate Protein; D005982:Glutathione Transferase; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D050737:Proto-Oncogene Proteins c-crk; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism*
C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D016023:Integrins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D019000:Phosphotyrosine; D005982:Glutathione Transferase; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases