Crosslinking and G-protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses

摘要: Tissue transglutaminase (TG2) affects cell-matrix interactions in cell spreading, migration and extracellular matrix (ECM) reorganisation. Using fibroblasts deficient TG2 or overexpressing normal crosslinking-deficient enzyme, we show that the crosslinking activity intracellular G-protein function signal transduction contribute differentially to regulation of interactions. TG2-deficient cells displayed attachment but delayed spreading on ECM substrata defects motility unrelated crosslinking. Blocking antibodies failed induce similar fibroblasts. had focal adhesion turnover stress fibre formation, showed changes kinase (FAK) phosphorylation activate protein C α (PKCα). Phospholipase (PLC) PKCα inhibitors blocked whilst PKC activators induced cells. In contrast, remodelling was not only compromised by deficiency also overexpression dominant negative enzyme TG inhibitors. increased tension required for membrane type 1-MMP (MT1-MMP)-dependent activation MMP-2. Our results demonstrate is involved control dynamic formation via phospholipase activity. By virtue its activity, plays a central role regulating remodelling.