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

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.

Publication DOI: https://doi.org/10.1074/jbc.M801763200
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > 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
Publication ISSN: 1083-351X
Last Modified: 29 Feb 2024 08:09
Date Deposited: 19 Aug 2019 08:51
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.jbc. ... nt/283/30/20937 (Publisher URL)
PURE Output Type: Article
Published Date: 2008-07-25
Authors: Telci, Dilek
Wang, Zhuo (ORCID Profile 0000-0002-2212-8318)
Li, Xiaoling
Verderio, Elisabetta A.M.
Humphries, Martin J.
Baccarini, Manuela
Basaga, Huveyda
Griffin, Martin (ORCID Profile 0000-0003-3824-306X)

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