A novel RGD-independent cel adhesion pathway mediated by fibronectin-bound tissue transglutaminase rescues cells from anoikis


Specific association of tissue transglutaminase (tTG) with matrix fibronectin (FN) results in the formation of an extracellular complex (tTG-FN) with distinct adhesive and pro-survival characteristics. tTG-FN supports RGD-independent cell adhesion of different cell types and the formation of distinctive RhoA-dependent focal adhesions following inhibition of integrin function by competitive RGD peptides and function blocking anti-integrin antibodies alpha5beta1. Association of tTG with its binding site on the 70-kDa amino-terminal FN fragment does not support this cell adhesion process, which seems to involve the entire FN molecule. RGD-independent cell adhesion to tTG-FN does not require transamidating activity, is mediated by the binding of tTG to cell-surface heparan sulfate chains, is dependent on the function of protein kinase Calpha, and leads to activation of the cell survival focal adhesion kinase. The tTG-FN complex can maintain cell viability of tTG-null mouse dermal fibroblasts when apoptosis is induced by inhibition of RGD-dependent adhesion (anoikis), suggesting an extracellular survival role for tTG. We propose a novel RGD-independent cell adhesion mechanism that promotes cell survival when the anti-apoptotic role mediated by RGD-dependent integrin function is reduced as in tissue injury, which is consistent with the externalization and binding of tTG to fibronectin following cell damage/stress.

Publication DOI: https://doi.org/10.1074/jbc.M303303200
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > Aston Pharmacy School
Aston University (General)
Additional Information: © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Uncontrolled Keywords: 3T3 cells,animals,anoikis,cell adhesion,cultured cells,cytoskeleton,fibroblasts,fibronectins,focal adhesions,guinea pigs,heparin,humans,mice,oligopeptides,osteoblasts,protein binding,protein kinase C,protein kinase C-alpha,proteoglycans,transglutaminases
Publication ISSN: 1083-351X
Last Modified: 09 May 2024 07:08
Date Deposited: 24 May 2012 12:17
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Related URLs: http://www.jbc. ... nt/278/43/42604 (Publisher URL)
PURE Output Type: Article
Published Date: 2003-10-24
Authors: Verderio, Elisabetta A.M.
Telci, Dilek
Okoye, Afam
Melino, Gerry
Griffin, Martin (ORCID Profile 0000-0003-3824-306X)



Version: Published Version

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