Fibronectin-tissue transglutaminase matrix rescues RGD-impaired celladhesion through syndecan-4 and β integrin co-signaling

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Authors

  • Dilek Telci
  • Zhuo Wang
  • Xiaoling Li
  • Elisabetta A.M. Verderio
  • Martin J. Humphries
  • Manuela Baccarini
  • Huveyda Basaga
  • Martin Griffin

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Abstract

Heterotropic association of tissue transglutaminase (TG2) with extracellular matrix-associated fibronectin (FN) can restore the adhesion of fibroblasts when the integrin-mediated direct binding to FN is impaired using RGD-containing peptide. We demonstrate that the compensatory effect of the TG-FN complex in the presence of RGD-containing peptides is mediated by TG2 binding to the heparan sulfate chains of the syndecan-4 cell surface receptor. This binding mediates activation of protein kinase Ca (PKCa) and its subsequent interaction with ß1 integrin since disruption of PKCa binding to ß1 integrins with a cell-permeant competitive peptide inhibits cell adhesion and the associated actin stress fiber formation. Cell signaling by this process leads to the activation of focal adhesion kinase and ERK1/2 mitogen-activated protein kinases. Fibroblasts deficient in Raf-1 do not respond fully to the TG-FN complex unless either the full-length kinase competent Raf-1 or the kinase-inactive domain of Raf-1 is reintroduced, indicating the involvement of the Raf-1 protein in the signaling mechanism. We propose a model for a novel RGD-independent cell adhesion process that could be important during tissue injury and/or remodeling whereby TG-FN binding to syndecan-4 activates PKCa leading to its association with ß1 integrin, reinforcement of actin-stress fiber organization, and MAPK pathway activation.

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Details

Original languageEnglish
Pages (from-to)20937-20947
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number30
DOIs
Publication statusPublished - 25 Jul 2008

Bibliographic note

© 2008 The American Society for Biochemistry and Molecular Biology, Inc.

    Keywords

  • nicotinic acetylcholine receptor, nAChR, Na, K-ATPase functionally, skeletal muscle, binding, nanomolar concentrations, electrogenic transport, K-ATPase α2 isozyme, membrane hyperpolarization, neuromuscular transmission, muscle excitation

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