title: Cysteine array matrix metalloproteinase (CA-MMP)/MMP-23 is a type II transmembrane matrix metalloproteinase regulated by a single cleavage for both secretion and activation.
abstract: Matrix metalloproteinases characterized so far are either secreted or membrane anchored via a type I transmembrane domain or a glycosylphosphatidylinositol linkage. Lacking either membrane-anchoring mechanism, the newly discovered CA-MMP/MMP-23 was reported to be expressed as a cell-associated protein. In this report, we present evidence that CA-MMP is expressed as an integral membrane zymogen with an N-terminal signal anchor, and secreted as a fully processed mature enzyme. We further demonstrate that L(20)GAALSGLCLLSALALL(36) is required for this unique membrane localization as a signal anchor and its secretion is regulated by a proprotein convertase motif RRRR(79) sandwiched between its pro- and catalytic domains. Thus, CA-MMP is a type II transmembrane MMP that can be regulated by a single proteolytic cleavage for both activation and secretion, establishing a novel paradigm for protein trafficking and processing within the secretory pathway.
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA. peixx003@tc.umn.edu
authors.forename: D
authors.initials: D
authors.lastname: Pei
authors.forename: T
authors.initials: T
authors.lastname: Kang
authors.forename: H
authors.initials: H
authors.lastname: Qi
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000737:chemistry; D006031:Glycosylation; D006056:Golgi Apparatus / Q000737:chemistry; D020782:Matrix Metalloproteinases; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D021382:Protein Sorting Signals / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D021382:Protein Sorting Signals; C492180:MMP23A protein, human; C117705:MMP23B protein, human; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases