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  • 标题:Src kinase activation by direct interaction with the integrin β cytoplasmic domain
  • 本地全文:下载
  • 作者:Elena G. Arias-Salgado ; Sergio Lizano ; Sugata Sarkar
  • 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.
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