Leukolysin/MMP25/MT6-MMP: a novel matrix metalloproteinase specifically expressed in the leukocyte lineage.
A novel matrix metalloproteinase (MMP) was identified from leukocytes and found to be specifically expressed by peripheral blood leukocytes among 29 different tissues examined. Named leukolysin, it encodes for 562 residues with a conserved MMP structure, i.e., pre-, pro-, catalytic, hinge- and hemopexin-like domains, but also a RXK/RR motif, known for its role in MMP zymogen activation, and a C-terminal hydrophobic segment. Overall, leukolysin displays the strongest homology to the newly identified MT-MMP subgroup with 45% and 39% identities to MT4- and MT1-MMPs vs 30% and 31.5% to MMP1 and 3 respectively. Unlike MT4-MMP whose proteolytic activity remains undefined, a C-terminally truncated leukolysin is expressed as a strong gelatinolytic species at 28 kDa which is derived from a cell-associated 34 kDa proenzyme, presumably by furin or proprotein convertase mediated removal of the propeptide (approximately 6 kDa). By green fluorescent protein (GFP) tagging, the intracellular proenzyme is localized to granules throughout the cell, suggesting that activation occur immediately prior to secretion. Taken together, leukolysin may be part of the proteolytic arsenal deployed by leukocytes during inflammatory responses. Molecular cloning of a novel MMP: MMP:25
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Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA. peixx003@tc.umn.edu
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D019070:Cell Lineage; D003594:Cytoplasmic Granules / Q000201:enzymology; D018076:DNA, Complementary; D004285:Dogs; D004792:Enzyme Precursors / Q000378:metabolism; D058851:GPI-Linked Proteins; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D020782:Matrix Metalloproteinases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D014018:Tissue Distribution
D018076:DNA, Complementary; D004792:Enzyme Precursors; D058851:GPI-Linked Proteins; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; C403928:matrix metalloproteinase 25