Fibronectin-tissue transglutaminase matrix rescues RGD-impaired cell adhesion through syndecan-4 and β1 integrin co-signaling

Telci, D, Wang, Z, Verderio, E ORCID: 0000-0001-9153-8997, Humphries, MJ, Baccarini, M, Basaga, H and Griffin, M, 2008. Fibronectin-tissue transglutaminase matrix rescues RGD-impaired cell adhesion through syndecan-4 and β1 integrin co-signaling. Journal of Biological Chemistry, 283 (30), pp. 20937-20947.

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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 Cα (PKCα) and its subsequent interaction with β1 integrin since disruption of PKCα binding to β1 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 PKCα leading to its association with β1 integrin, reinforcement of actin-stress fiber organization, and MAPK pathway activation.

Item Type: Journal article
Publication Title: Journal of Biological Chemistry
Creators: Telci, D., Wang, Z., Verderio, E., Humphries, M.J., Baccarini, M., Basaga, H. and Griffin, M.
Publisher: American Society for Biochemistry and Molecular Biology
Date: 2008
Volume: 283
Number: 30
Rights: Copyright © 2008 by American Society for Biochemistry and Molecular Biology.
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 10:15
Last Modified: 09 Jun 2017 13:23

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