RGD Reference Report - Cleavage of focal adhesion kinase in vascular smooth muscle cells overexpressing membrane-type matrix metalloproteinases. - Rat Genome Database

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Cleavage of focal adhesion kinase in vascular smooth muscle cells overexpressing membrane-type matrix metalloproteinases.

Authors: Shofuda, T  Shofuda, K  Ferri, N  Kenagy, RD  Raines, EW  Clowes, AW 
Citation: Shofuda T, etal., Arterioscler Thromb Vasc Biol. 2004 May;24(5):839-44. Epub 2004 Mar 25.
RGD ID: 1582604
Pubmed: (View Article at PubMed) PMID:15044209
DOI: Full-text: DOI:10.1161/01.ATV.0000126680.78500.4c

BACKGROUND: Membrane-type matrix metalloproteinases (MT-MMPs) were initially identified as cell surface activators of MMP-2 (gelatinase A). We have reported that MT1-MMPs and MT3-MMPs are expressed by activated vascular smooth muscle cells (SMCs) and play a role in the regulation of cell function. Overexpression of MT-MMPs results in cell rounding, decreased adherence, and increased migration. Because integrin-mediated cell adhesion regulates these events, we have investigated the functional relationship between MT-MMPs and focal adhesion assembly. METHODS AND RESULTS: Using adenoviral vectors we show that overexpression of MT-MMPs reduces the number of focal contacts, whereas the cell surface expression of integrin subunits remains unchanged. The 125-kDa focal adhesion kinase (FAK) is cleaved resulting in a 90-kDa fragment under these conditions, and paxillin is partially dissociated from FAK after its cleavage. Pretreatment of cells with BB94, a synthetic MMP inhibitor, rescues cell adhesion and prevents changes in focal adhesions, supporting a potential role for MT-MMP enzymatic activities. CONCLUSIONS: This study provides the first evidence that MT-MMPs are not only important in matrix degradation but also may affect the function of focal adhesions through FAK cleavage.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Mmp14  (matrix metallopeptidase 14)


Additional Information