Price L S, Leng J, Schwartz M A, Bokoch G M
Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Mol Biol Cell. 1998 Jul;9(7):1863-71. doi: 10.1091/mbc.9.7.1863.
Adhesion to ECM is required for many cell functions including cytoskeletal organization, migration, and proliferation. We observed that when cells first adhere to extracellular matrix, they spread rapidly by extending filopodia-like projections and lamellipodia. These structures are similar to the Rac- and Cdc42-dependent structures observed in growth factor-stimulated cells. We therefore investigated the involvement of Rac and Cdc42 in adhesion and spreading on the ECM protein fibronectin. We found that integrin-dependent adhesion led to the rapid activation of p21-activated kinase, a downstream effector of Cdc42 and Rac, suggesting that integrins activate at least one of these GTPases. Dominant negative mutants of Rac and Cdc42 inhibit cell spreading in such a way as to suggest that integrins activate Cdc42, which leads to the subsequent activation of Rac; both GTPases then contribute to cell spreading. These results demonstrate that initial integrin-dependent activation of Rac and Cdc42 mediates cell spreading.
许多细胞功能，包括细胞骨架组织、迁移和增殖，都需要细胞与细胞外基质（ECM）黏附。我们观察到，当细胞首次黏附到细胞外基质时，它们会通过伸出丝状伪足样突起和片状伪足迅速铺展。这些结构类似于在生长因子刺激的细胞中观察到的依赖Rac和Cdc42的结构。因此，我们研究了Rac和Cdc42在细胞黏附到ECM蛋白纤连蛋白并铺展过程中的作用。我们发现，整合素依赖性黏附导致p21活化激酶（Cdc42和Rac的下游效应器）迅速活化，这表明整合素激活了这些小GTP酶中的至少一种。Rac和Cdc42的显性负性突变体以一种表明整合素激活Cdc42从而导致随后Rac激活的方式抑制细胞铺展；然后这两种小GTP酶都促进细胞铺展。这些结果表明，Rac和Cdc42最初依赖整合素的激活介导了细胞铺展。
