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

Telci, Dilek, Wang, Zhuo, Li, Xiaoling, Verderio, Elisabetta A.M., Humphries, Martin J., Baccarini, Manuela, Basaga, Huveyda and Griffin, Martin (2008). Fibronectin-tissue transglutaminase matrix rescues RGD-impaired celladhesion through syndecan-4 and β integrin co-signaling. Journal of Biological Chemistry, 283 (30), pp. 20937-20947.


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.

Publication DOI:
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences > Biosciences
Life & Health Sciences > Chronic and Communicable Conditions
Life & Health Sciences
Life & Health Sciences > Cellular and Molecular Biomedicine
Aston University (General)
Additional Information: © 2008 The American Society for Biochemistry and Molecular Biology, Inc.
Uncontrolled 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,Biochemistry,Cell Biology,Molecular Biology
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.jbc. ... nt/283/30/20937 (Publisher URL)
Published Date: 2008-07-25
Authors: Telci, Dilek
Wang, Zhuo
Li, Xiaoling
Verderio, Elisabetta A.M.
Humphries, Martin J.
Baccarini, Manuela
Basaga, Huveyda
Griffin, Martin



Version: Published Version

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