Wary K K, Mainiero F, Isakoff S J, Marcantonio E E, Giancotti F G
Department of Pathology and Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
Cell. 1996 Nov 15;87(4):733-43. doi: 10.1016/s0092-8674(00)81392-6.
We provide evidence that a class of integrins combines with the adaptor Shc and thereby with Grb2. Coimmunoprecipitation and mutagenesis experiments indicate that the recruitment of Shc is specified by the extracellular or transmembrane domain of integrin alpha subunit and suggest that this process is mediated by caveolin. Mutagenesis and dominant-negative inhibition studies reveal that Shc is necessary and sufficient for activation of the MAP kinase pathway in response to integrin ligation. Mitogens and Shc-activating integrins cooperate to promote transcription from the Fos serum response element and transit through G1. In contrast, adhesion mediated by integrins not linked to Shc results in cell cycle arrest and apoptosis even in presence of mitogens. These findings indicate that the association of specific integrins with Shc regulates cell survival and cell cycle progression.
我们提供的证据表明，一类整合素与衔接蛋白Shc结合，进而与Grb2结合。免疫共沉淀和诱变实验表明，Shc的募集由整合素α亚基的细胞外或跨膜结构域决定，并提示该过程由小窝蛋白介导。诱变和显性负抑制研究表明，Shc对于整合素连接后激活丝裂原活化蛋白激酶（MAP）途径是必要且充分的。有丝分裂原和激活Shc的整合素协同作用，促进从Fos血清反应元件的转录并通过G1期。相反，即使在有丝分裂原存在的情况下，由不与Shc相连的整合素介导的黏附也会导致细胞周期停滞和凋亡。这些发现表明，特定整合素与Shc的结合调节细胞存活和细胞周期进程。
