Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue transglutaminase (TG2) affects cell-matrix interactions in cell spreading, migration and extracellular matrix (ECM) reorganisation. Using fibroblasts deficient in TG2 or overexpressing normal or crosslinking-deficient enzyme, we show that the extracellular crosslinking activity and intracellular G-protein function in signal transduction contribute differentially to regulation of cell-matrix interactions. TG2-deficient cells displayed normal attachment but delayed spreading on ECM substrata and defects in motility unrelated to crosslinking. Blocking antibodies to TG2 failed to induce similar defects in normal fibroblasts. TG2-deficient fibroblasts had defects in focal adhesion turnover and stress fibre formation, showed changes in focal adhesion kinase (FAK) phosphorylation and failed to activate protein kinase C alpha (PKCalpha). Phospholipase C (PLC) and PKCalpha inhibitors blocked spreading of normal fibroblasts whilst PKC activators induced spreading in TG2-deficient cells. In contrast, ECM remodelling was not only compromised by TG2 deficiency but also by overexpression of dominant negative enzyme and TG inhibitors. TG2 activity increased matrix tension and was required for membrane type 1-MMP (MT1-MMP)-dependent activation of MMP-2. Our results demonstrate that TG2 is involved in the control of dynamic adhesion formation in cell spreading and migration via regulation of phospholipase C activity. By virtue of its crosslinking activity, the enzyme plays a central role in regulating ECM remodelling.
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PMID:Crosslinking and G-protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses. 1519 98

Transfection of the estrogen dependent and poorly invasive MCF-7 cell line to overexpress erbB2 was reported to increase athymic nude mouse mammary fat pad tumor growth; similar PKC-alpha overexpression produced a rapidly growing and metastatic transfectant. We investigated the invasive capacities of the two transfectants in vitro, their secretion of the proteolytic enzymes metalloproteinase (MMP)-9 and -2 and urokinase-type plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1), together with membrane uPA receptor (uPAR) levels as determined by ELISA. Compared with the MCF-7 cells, the erbB2 transfectant was more invasive and secreted higher levels of MMP-9 and uPA; also there was a greatly enhanced PAI-1 secretion and cellular uPAR expression. The PKC-alpha transfectant cells secreted extremely high levels of uPA and some MMP-9 and MMP-2, with an intermediate increase in uPAR; however, they were so poorly adherent that it was not possible to assess invasiveness in vitro. Thus, erbB2-overexpressing MCF-7 cells possessed several features associated with the invasive phenotype. The reportedly aggressive metastatic phenotype induced by PKC-alpha overexpression, however, was notable only for its uPA hypersecretion.
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PMID:Expression of the invasive phenotype by MCF-7 human breast cancer cells transfected to overexpress protein kinase C-alpha or the erbB2 proto-oncogene. 2153 46