Fibronectin matrix regulates activation of RHO and CDC42 GTPases and cell cycle progression

Sandrine Bourdoulous, Gertraud Orend, Deidre A. MacKenna, Renata Pasqualini, Erkki Ruoslahti

Research output: Contribution to journalArticle

192 Scopus citations

Abstract

Adherent cells assemble fibronectin into a fibrillar matrix on their apical surface. The fibril formation is initiated by fibronectin binding to the integrins α5β1 and αvβ3, and is completed by a process that includes fibronectin self-assembly. We found that a 76-amino acid fragment of fibronectin (III1-C) that forms one of the self-assembly sites caused disassembly of preformed fibronectin matrix without affecting cell adhesion. Treating attached fibroblasts or endothelial cells with III1-C inhibited cell migration and proliferation. Rho-dependent stress fiber formation and Rho- dependent focal contact protein phosphorylation were also inhibited, whereas Cdc42 was activated, leading to actin polymerization into filopodia. ACK (activated Cdc42-binding kinase) and p38 MAPK (mitogen-activated protein kinase), two downstream effectors of Cdc42, were activated, whereas PAK (p2- activated kinase) and JNK/SAPK (c-Jun NH2-terminal kinase/stress-activated protein kinase) were inhibited. III1-C treatment also modulated activation of JNK and ERK (extracellular Signal-regulated kinases) in response to growth factors, and reduced the activity of the cyclin E-cdk2 complex. These results indicate that the absence of fibronectin matrix causes activation of Cdc42, and that fibronectin matrix is required for Rho activation and cell cycle progression.

Original languageEnglish (US)
Pages (from-to)267-276
Number of pages10
JournalJournal of Cell Biology
Volume143
Issue number1
DOIs
StatePublished - Oct 5 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

Keywords

  • Cyclin E-cdk2
  • Extracellular matrix
  • F-actin
  • Mitogen-activated protein kinase (MAPK)
  • Signal transduction

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