Integrins and Src: dynamic duo of adhesion signaling.
Src family protein tyrosine kinases (SFKs) play important roles downstream of integrin adhesion receptors, and they are necessary for the generation of "outside-in signals" that regulate cytoskeletal organization, cell motility and gene expression in response to cell adhesion. One relatively under-explored facet of this relationship is the possible physical interaction of integrins with SFKs. Recently, it has been established that beta3 integrins and c-Src can interact directly, and this pool of c-Src is activated by cell adhesion to initiate outside-in signaling in platelets, osteoclasts and cells of the vasculature. Here, the biochemical basis for and biological significance of this integrin-SFK interaction is summarized, and I propose a general mechanism for initiation of outside-in integrin signaling.
Shattil
Sanford J
SJ
Hematology-Oncology Division, Department of Medicine, University of California-San Diego, La Jolla, CA 92093, USA. sshattil@ucsd.edu
D000818:Animals; D002448:Cell Adhesion; D016023:Integrins / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D016023:Integrins; D019061:src-Family Kinases