Transglutaminase-mediated oligomerization of the fibrin(ogen) αC domains promotes integrin-dependent cell adhesion and signaling Article

Belkin, AM, Tsurupa, G, Zemskov, E et al. (2005). Transglutaminase-mediated oligomerization of the fibrin(ogen) αC domains promotes integrin-dependent cell adhesion and signaling . BLOOD, 105(9), 3561-3568. 10.1182/blood-2004-10-4089

cited authors

  • Belkin, AM; Tsurupa, G; Zemskov, E; Veklich, Y; Weisel, JW; Medved, L

authors

abstract

  • Interactions of endothelial cells with fibrin(ogen) are implicated in inflammation, angiogenesis, and wound healing. Cross-linking of the fibrinogen αC domains with factor XIIIa generates ordered αC oligomers mimicking polymeric arrangement of the αC domains in fibrin. These oligomers and those prepared with tissue transglutaminase were used to establish a mechanism of the αC domain-mediated interaction of fibrin with endothelial cells. Cell adhesion and chemical cross-linking experiments revealed that oligomerization of the αC domains by both transglutaminases significantly increases their RGD (arginyl-glycyl-aspartate)-dependent interaction with endothelial αVβ3 and to a lesser extent with αVβ5 and α5β1 integrins. The oligomerization promotes integrin clustering, thereby increasing cell adhesion, spreading, formation of prominent peripheral focal contacts, and integrin-mediated activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) signaling pathways. The enhanced integrin clustering is likely caused by ordered juxtaposition of RGD-containing integrin-binding sites upon oligomerization of the αC domains and increased affinity of these domains for integrins. Our findings provide new insights into the mechanism of the αC domain-mediated interaction of endothelial cells with fibrin and imply its potential involvement in cell migration. They also suggest a new role for transglutaminases in regulation of integrin-mediated adhesion and signaling via covalent modification of integrin ligands. © 2005 by The American Society of Hematology.

publication date

  • May 1, 2005

published in

Digital Object Identifier (DOI)

start page

  • 3561

end page

  • 3568

volume

  • 105

issue

  • 9