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Membrane type-matrix metalloproteinases (MT-MMP)

2003; Elsevier BV; Linguagem: Inglês

10.1016/s0070-2153(03)54004-2

1557-8933

Stanley Zucker, Duanqing Pei, Jian Cao, Carlos López‐Otín,

Blood Coagulation and Thrombosis Mechanisms

Matrix metalloproteinases (MMPs) belong to the family of zinc endopeptidases collectively referred to as metzincins. The metzincin superfamily is distinguished by a highly conserved motif containing three histidines that bind zinc at the catalytic site and a conserved methionine that sits beneath the active site. The metzincins are subdivided into four multigene families: serralysins, astacins, ADAMs/adamalysins, and MMPs. Once activated, MMPs degrade a variety of extracellular matrix components and assorted other proteins including growth factors, growth factor binding proteins, and protease inhibitors. The ability to degrade extracellular matrix proteins is essential for any cell to interact properly with its immediate surroundings and for multicellular organisms to develop and function normally. MMPs also generate matrix protein fragments, which have functional activity of their own. These various functions of MMPs modulate cell invasion and metastasis, cell migration, apoptosis, and angiogenesis. The belief that an MMP is involved in a given biologic/pathologic process is often based on the strength of its association with that process and the existence of plausible mechanisms that can be tested by experimental approaches. Because of extensive redundancy of MMP function in animals, it has been difficult to appreciate the role of individual genes in various experimental models. The multiplicity of MMPs with distinct but somewhat overlapping functions appears to act as a safeguard against loss of regulatory control. The known MMP genes have been divided into four subfamilies based on gene structure. Group I consists of the collagenase subfamily. Group 2 consists of the gelatinases/modular alteration (fimodular a-like domains) subfamily. Group 3 consists of the variant hemopexin exon subfamily. Group 4 consists of the variant catalytic exon and unique 3′-end exon (plasma membrane and cytoplasmic domains) subfamily, which consists of the membrane type-matrix metalloproteinases (MT-MMPs).