Discoidin domain receptor 1 activation suppresses α2b 1 integrin-dependent cell spreading through inhibition of Cdc42 sctivity

Y. E.H. Yi-Chun, Chau Zen Wang, Ming Jer Tang

研究成果: Article同行評審

52 引文 斯高帕斯(Scopus)

摘要

Upregulation and overexpression of discoidin domain receptor I (DDRI) have been implied in the regulation of kidney development and progression of cancers. Our previous studies with Mardin-Darby canine kidney (MDCK) cells showed that overexpression of DDRI inhibited cell spreading, whereas dominant negative DDRI promoted cell spreading on collagen-coated dish. Cell spreading is an important characteristic for cell differentiation and survival. However, little is known about the molecular mechanisms underlying the role of DDRI in cell spreading. We have found here a novel signaling pathway of DDRI consisting of Cdc42 that regulates the assembly and disassembly of cytoskeleton and cell spreading in MDCK cells. Cell spreading involves the organization of cytoskeleton that is mainly regulated by Rho-family GTPases. We assessed the activity of Rho-family GTPases and transfected MDCK cells with constitutively active or dominant negative GTPases, and quantified the extent of cell spreading. These results showed that DDRI decreased the filamentous actin ratio and Racl/Cdc42 activities, but had no effects on RhoAactivity. Neither constitutively active nor dominant negative Racl altered DDRI-inhibited cell spreading. Constitutively active Cdc42 could rescue the DDRI-inhibited cell spreading, whereas dominant negative Cdc42 inhibited cell spreading, indicating that DDRI-inhibited cell spreading is Cdc42 dependent. With the use of α2β l integrin blocking antibody, we showed that collagen-induced Cdc42 activation was mediated by α2βl integrin. Moreover, ectopic FAK expression enhanced the Cdc42 activity. Reducing FAK activity by dominant negative FAK (FRNK) markedly abolished the Cdc42 activity. These findings show that DDRIa/b activation inhibits cell spreading through suppressing α2βlintegrin-mediated Cdc42 activation.

原文English
頁(從 - 到)146-156
頁數11
期刊Journal of Cellular Physiology
218
發行號1
DOIs
出版狀態Published - 2009 1月

All Science Journal Classification (ASJC) codes

  • 生理學
  • 臨床生物化學
  • 細胞生物學

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