SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility
SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility
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DOI：
10.1093/emboj/19.24.6721
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发表时间：
2000-12-15
期刊：
影响因子：
11.4
通讯作者：
Kasuga, M
中科院分区：
文献类型：
--
作者：
Inagaki, K;Yamao, T;Kasuga, M
跨膜糖蛋白SHPS-1结合蛋白酪氨酸磷酸酶SHP-2并作为其底物。虽然SHPS-1与生长因子和细胞粘附诱导的信号传导有关，但其生物学作用仍不清楚。成纤维细胞纯合的SHPS-1突变体缺乏这种蛋白质的大部分细胞质区域的表达表现出增加的肌动蛋白应力纤维和局灶性粘连的形成。它们比野生型细胞在纤连蛋白上传播得更快，但在随后的极化延伸和迁移中有缺陷。粘附诱导的Rho激活的程度，但不是Rac的，也显着减少的突变细胞。Ras-细胞外信号调节激酶信号通路和c-Jun N-末端激酶通过生长因子的激活在突变成纤维细胞中不受影响或增强。这些结果表明，SHPS-1起着至关重要的作用，在整合素介导的细胞骨架重组，细胞运动和Rho的调节，它也负调节生长因子诱导的有丝分裂原活化蛋白激酶的激活。
The transmembrane glycoprotein SHPS-1 binds the protein tyrosine phosphatase SHP-2 and serves as its substrate. Although SHPS-1 has been implicated in growth factor- and cell adhesion-induced signaling, its biological role has remained unknown. Fibroblasts homozygous for expression of an SHPS-1 mutant lacking most of the cytoplasmic region of this protein exhibited increased formation of actin stress fibers and focal adhesions. They spread more quickly on fibronectin than did wild-type cells, but they were defective in subsequent polarized extension and migration. The extent of adhesion-induced activation of Rho, but not that of Rac, was also markedly reduced in the mutant cells. Activation of the Ras-extracellular signal-regulated kinase signaling pathway and of c-Jun N-terminal kinases by growth factors was either unaffected or enhanced in the mutant fibroblasts. These results demonstrate that SHPS-1 plays crucial roles in integrin-mediated cytoskeletal reorganization, cell motility and the regulation of Rho, and that it also negatively modulates growth factor-induced activation of mitogen-activated protein kinases.