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A Novel RGD-independent Cell Adhesion Pathway Mediated by Fibronectin-bound Tissue Transglutaminase Rescues Cells from Anoikis
- Source :
- Journal of Biological Chemistry. 278:42604-42614
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- 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.
- Subjects :
- Protein Kinase C-alpha
Tissue transglutaminase
Guinea Pigs
Integrin
Biochemistry
Focal adhesion
Mice
Cell Adhesion
Animals
Humans
Cell adhesion
Molecular Biology
Cells, Cultured
Cytoskeleton
Protein Kinase C
Focal Adhesions
Osteoblasts
Transglutaminases
biology
Heparin
Cell adhesion molecule
3T3 Cells
Cell Biology
Fibroblasts
Anoikis
Molecular biology
Fibronectins
Cell biology
Cell Adhesion Process
Fibronectin
biology.protein
Proteoglycans
Neural cell adhesion molecule
Oligopeptides
Protein Binding
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 278
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....f7a6708f85103581bd825cf8bc1496ec