p-SHC1 binds integrin alpha5beta1:fibronectin

Estradiol treatment of human breast cancer cells stimulates GPER1-dependent formation of integrin alpha5 beta1:fibronectin (FN):phosphorylated SHC1 complexes in a SRC- and G-protein beta gamma-dependent fashion (Quinn et al, 2009). Formation of integrin:fibronectin fibrils has been shown to enhance anchorage independent growth (Salnier et al, 1996; Qiao et al, 2000; Quinn et al, 2009). Formation of a fibronectin:integrin matrix is required for estradiol-stimulated EGFR phosphorylation, and consistent with this, EGFR phosphorylation is inhibited after treatment of cells with either soluble FN peptide fragments or antibody that blocks the integrin alpha5beta1:fibronectin interaction (Quinn et al, 2009; reviewed in Prossnitz and Barton, 2014). Although SHC is known to have roles downstream of activated EGFR, EGFR phosphorylation after estradiol stimulation is abrogated in the inactive SHC Y317F mutant, suggesting that SHC acts upstream of EGFR in this pathway. In contrast, SHC phosphorylation is not required for the interaction with integrin alpha5beta1 (Quinn et al, 2009).<br><br><br>

雌激素对人乳腺癌细胞的处理可刺激GPER1依赖性整合素α5β1:纤连蛋白(FN):磷酸化SHC1复合物的形成，此过程依赖于SRC和G蛋白βγ亚基。整合素与纤连蛋白纤丝的形成已被证实可增强非附着性生长（Salnier等，1996；Qiao等，2000；Quinn等，2009）。形成纤连蛋白:整合素基质对于雌激素诱导的EGFR磷酸化是必需的，与此一致，用可溶性FN肽片段或阻断整合素α5β1:纤连蛋白相互作用的抗体处理细胞后，EGFR磷酸化受到抑制（Quinn等，2009；Prossnitz和Barton，2014年综述）。尽管已知SHC在激活EGFR下游具有作用，但雌激素刺激后EGFR磷酸化在非活性SHC Y317F突变体中被消除，这表明SHC在此通路中位于EGFR上游。相反，SHC磷酸化对于与整合素α5β1的相互作用并非必需（Quinn等，2009）。