Auger K R, Songyang Z, Lo S H, Roberts T M, Chen L B
Division of Cellular and Molecular Biology, Dana Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 1996 Sep 20;271(38):23452-7. doi: 10.1074/jbc.271.38.23452.
Tensin is an SH2 domain-containing cytoskeletal protein that binds to and caps actin filaments. Investigation of signal transduction mechanisms associated with tensin revealed the presence of phosphoinositide 3-kinase (PI 3-kinase) activity in tensin immunoprecipitates from platelet-derived growth factor-treated cells. Association of PI 3-kinase activity with tensin was transitory, and the amount of activity was approximately 1% of the total PI 3-kinase activity found in anti-phosphotyrosine (anti-pY) immunoprecipitates. In vitro, PI 3-kinase activity associated with the SH2 domain of tensin in a platelet-derived growth factor-dependent manner. The optimal phosphopeptide binding specificity of the SH2 domain of tensin was determined to be phospho-Y (E or D), N, (I, V, or F). Synthetic phosphopeptides containing the sequence YENI could specifically block the association of PI 3-kinase activity with tensin in a dose-dependent manner. These results suggest that PI 3-kinase interacts with the cytoskeleton via the SH2 domain of tensin and may play an important role in platelet-derived growth factor-induced cytoskeletal reorganization that is concomitant with cell migration and proliferation.
张力蛋白是一种含SH2结构域的细胞骨架蛋白，可与肌动蛋白丝结合并封端。对与张力蛋白相关的信号转导机制的研究表明，在血小板衍生生长因子处理的细胞的张力蛋白免疫沉淀物中存在磷酸肌醇3激酶（PI 3激酶）活性。PI 3激酶活性与张力蛋白的结合是短暂的，其活性量约为抗磷酸酪氨酸（抗pY）免疫沉淀物中发现的总PI 3激酶活性的1%。在体外，PI 3激酶活性以血小板衍生生长因子依赖的方式与张力蛋白的SH2结构域结合。张力蛋白SH2结构域的最佳磷酸肽结合特异性被确定为磷酸化-Y（E或D）、N、（I、V或F）。含有序列YENI的合成磷酸肽可以剂量依赖的方式特异性阻断PI 3激酶活性与张力蛋白的结合。这些结果表明，PI 3激酶通过张力蛋白的SH2结构域与细胞骨架相互作用，可能在血小板衍生生长因子诱导的细胞骨架重组中起重要作用，而细胞骨架重组与细胞迁移和增殖同时发生。
