期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：23
页码：13298-13302
DOI：10.1073/pnas.2336149100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Src tyrosine kinases transmit integrin-dependent signals pivotal for cell movement and proliferation. Here, we establish a mechanism for Src activation by integrins. c-Src is shown to bind constitutively and selectively to {beta}3 integrins through an interaction involving the c-Src SH3 domain and the carboxyl-terminal region of the {beta}3 cytoplasmic tail. Clustering of {beta}3 integrins in vivo activates c-Src and induces phosphorylation of Tyr-418 in the c-Src activation loop, a reaction essential for adhesion-dependent phosphorylation of Syk, a c-Src substrate. Unlike c-Src, Hck, Lyn, and c-Yes bind more generally to {beta}1A, {beta}2, and {beta}3 cytoplasmic tails. These results invoke a model whereby Src is primed for activation by direct interaction with an integrin {beta} tail, and integrin clustering stabilizes activated Src by inducing intermolecular autophosphorylation. The data provide a paradigm for integrin regulation of Src and a molecular basis for the similar functional defects of osteoclasts or platelets from mice lacking {beta}3 integrins or c-Src.
