Regulatory role for Src and phosphatidylinositol 3-kinase in initiation of fibronectin matrix assembly

Iwona Wierzbicka-Patynowski, Jean E. Schwarzbauer

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Fibronectin (FN) matrix assembly is a tightly regulated stepwise process that is initiated by interactions between FN and cell surface integrin receptors. These interactions activate many intracellular signaling pathways that regulate processes such as cell adhesion, migration, and survival. Here we demonstrate that cells lacking Src family kinases showed reduced ability to assemble FN fibrils as detected by immunofluorescence and by analysis of detergent extracts. The amount of FN matrix was further reduced by treatment with the phosphatidylinositol 3 (PI 3-kinase) inhibitor, wortmannin. CHOα5 cells, which are dependent on exogenous FN to initiate fibril formation, also showed significant reductions in matrix when treated with inhibitors of Src and PI 3-kinase. Combination of both inhibitors showed an additive inhibitory effect on assembly, which was concomitant with a loss of focal adhesion kinase phosphorylation. Decreased binding of the 70-kDa amino-terminal FN fragment at matrix assembly sites further supports a role for these kinases early during the process. We propose that these two signaling molecules, which lie downstream of integrins and focal adhesion kinase, are essential for efficient initiation of FN matrix assembly.

Original languageEnglish (US)
Pages (from-to)19703-19708
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number22
DOIs
StatePublished - May 31 2002

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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