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

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

Research output: Contribution to journalArticle

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

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Syndecan-4
Fibronectins
Integrins
Proto-Oncogene Proteins c-raf
Protein Kinases
Stress Fibers
Chemical activation
Cell adhesion
Fibroblasts
Cell Adhesion
Peptides
Actins
Focal Adhesion Kinase 2
Association reactions
Cell signaling
Focal Adhesion Protein-Tyrosine Kinases
Heparitin Sulfate
Fibers
Mitogen-Activated Protein Kinase 1
Cell Surface Receptors

Bibliographical 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

Cite this

Telci, Dilek ; Wang, Zhuo ; Li, Xiaoling ; Verderio, Elisabetta A.M. ; Humphries, Martin J. ; Baccarini, Manuela ; Basaga, Huveyda ; Griffin, Martin. / Fibronectin-tissue transglutaminase matrix rescues RGD-impaired celladhesion through syndecan-4 and β integrin co-signaling. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 30. pp. 20937-20947.
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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; Griffin, Martin.

In: Journal of Biological Chemistry, Vol. 283, No. 30, 25.07.2008, p. 20937-20947.

Research output: Contribution to journalArticle

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T1 - Fibronectin-tissue transglutaminase matrix rescues RGD-impaired celladhesion through syndecan-4 and β integrin co-signaling

AU - Telci, Dilek

AU - Wang, Zhuo

AU - Li, Xiaoling

AU - Verderio, Elisabetta A.M.

AU - Humphries, Martin J.

AU - Baccarini, Manuela

AU - Basaga, Huveyda

AU - Griffin, Martin

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Y1 - 2008/7/25

N2 - 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.

AB - 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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KW - binding

KW - nanomolar concentrations

KW - electrogenic transport

KW - K-ATPase α2 isozyme

KW - membrane hyperpolarization

KW - neuromuscular transmission

KW - muscle excitation

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