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

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Telci, Dilek and Wang, Zhuo and Li, Li and Verderio, Elisabetta A. M. and Humphries, Martin J. and Baccarini, Manuela and Başağa, Hüveyda and Griffin, Martin (2008) Fibronectin-tissue transglutaminase matrix rescues RGD-impaired cell adhesion through Syndecan-4 and β1 Integrin co-signaling. The Journal of Biological Chemistry, 283 (30). pp. 20937-20947. ISSN 0021-9258

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Official URL: http://dx.doi.org/10.1074/jbc.M801763200

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 C{alpha} (PKC{alpha}) and its subsequent interaction with β1 integrin since disruption of PKC{alpha} 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 PKC{alpha} leading to its association with β1 integrin, reinforcement of actin-stress fiber organization, and MAPK pathway activation.

Item Type:Article
Subjects:UNSPECIFIED
ID Code:9577
Deposited By:Hüveyda Başağa
Deposited On:30 Oct 2008 19:04
Last Modified:19 Jul 2019 12:42

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