Activation of Rac and Cdc42 by integrins mediates cell spreading
Activation of Rac and Cdc42 by integrins mediates cell spreading
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DOI：
10.1091/mbc.9.7.1863
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发表时间：
1998-07-01
影响因子：
3.3
通讯作者：
Bokoch, GM
中科院分区：
文献类型：
--
作者：
Price, LS;Leng, J;Bokoch, GM
与ECM的粘附是许多细胞功能所必需的，包括细胞骨架组织、迁移和增殖。我们观察到，当细胞第一次粘附到细胞外基质时，它们通过延长丝状伪足样突起和板状伪足迅速扩散。这些结构类似于生长因子刺激的细胞中观察到的Rac和Cdc 42依赖性结构。因此，我们研究了Rac和Cdc 42参与ECM蛋白纤连蛋白的粘附和扩散。我们发现，整合素依赖性粘附导致p21激活激酶的快速激活，Cdc 42和Rac的下游效应，这表明整合素激活至少一个这些GTP酶。Rac和Cdc 42的显性负突变体以这样的方式抑制细胞铺展，从而表明整合素激活Cdc 42，这导致随后的Rac激活;然后两种GTP酶都有助于细胞铺展。这些结果表明，Rac和Cdc 42的初始整合素依赖性活化介导细胞铺展。
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.