Studies on integrinα3β1-mediated signaling

细胞与层粘连蛋白-10/11(α-10/11，LN-10/11)黏附所触发的LN-10/11(LN-10/11)与纤维连接蛋白(FN)黏附所触发的LN-10/11(LN-10/11)信号转导事件不同，LN-10/11(LN-10/11)与LN-10/11(LN-10/11)是细胞黏附与纤维连接蛋白(FN)黏附所触发的信号转导通路，而LN-10/11(LN-10/11)则是LN-10/11(LN-10/11)与LN-10/11(LN-10/11)黏附所触发的信号转导通路。细胞黏附LN-10/11(LN-10/11LN-10/11通过α3β1整合素依赖的途径激活Rac，而不是Rho，该途径涉及p130Cas-CrkII-DOCK18O复合体，从而通过促进片状脂体的形成而强烈地促进细胞迁移。另一方面，细胞内调控细胞存活的信号通路主要集中在两个不同的信号通路上，即PI 3-K/Akt和Meki/ERK。LN-10/11对血清剥夺诱导的细胞凋亡的抑制作用强于FN。PI3-激酶抑制剂Wortmannin可抑制LN-10I11的抗凋亡作用，而Meki抑制剂PD98059可抑制FN的抗凋亡作用。我们的结果提供了明确的证据，不同的信号通路导致细胞存活在不同的ECM配体上被激活。此外，整合素N-糖链的重塑也可以调节其配体结合和整合素介导的信号转导。由于层粘连蛋白是上皮基底膜的主要成分，我们的工作支持基底膜的功能是为上皮组织的建立和维持提供独特的细胞生存信号的观点。

The α3β1 integrin-mediated signaling events triggered by cell adhesion to laminin-10/11(LN-10/11) are quite different from those triggered by adhesion to fibronectin (FN). LN-10/11 preferentially activates Rac, but not Rho, through an α3β1 integrin-dependent pathway involving a p130Cas-CrkII-DOCK18O complex, thereby strongly promoting cell migration through enhanced formation of lamellipodia. On the other hand, the intracellular signaling pathways regulating cell survival focusing on two distinct signaling pathways involving PI 3-kinase/Akt and MEKi/ERK have been investigated. LN-10/11 is more potent than FN in suppressing apoptosis induced by serum deprivations The anti-apoptotic effects of LN-10I11 could be inhibited by the PI 3-kinase inhibitor wortmannin, whereas the anti-apoptotic effects of FN were inhibited by the MEKi inhibitor PD98059. Our results provide clear evidence that different signaling pathways leading to cell survival are activated, on different ECM ligands. Furthermore, remodeling of N-glycans of the integrin could also modulate its ligand binding and integrin-mediated signaling. Since laminins are the major components of the basement membrane of epithelium, our work supports the notion that a function of the basement membrane is to provide distinctive cell survival signals for establishment and maintenance of epithelial tissue.