title: Binding of MAGP2 to microfibrils is regulated by proprotein convertase cleavage.
abstract: MAGP2 is a small extracellular protein with both tumor angiogenesis and cell signaling activity. MAGP2 was originally isolated biochemically from microfibril-rich connective tissue. The localization of MAGP2 to microfibrils has been confirmed by both immunohistochemistry and immunogold electron microscopy. Whether MAGP2 binding to microfibrils is regulated post-translationally is still unclear, however, and a better understanding of this process would be instructive to understanding the angiogenesis and signaling functions ascribed to MAGP2. Here we show via immunofluorescence studies that the T3 cell line, derived from ovarian mouse tumor cells, produces abundant fibrillin-2 microfibrils to which MAGP2 can bind. Co-localization of MAGP2 and fibrillin-2 can be detected either when MAGP2 is overexpressed in, or exogenously introduced to, the cells. As expected, matrix association of MAGP2 required its conserved Matrix Binding Domain. Matrix association was positively regulated by proprotein convertase (PC) cleavage of MAGP2; mutation of the MAGP2 PC consensus site reduced the amount of matrix-associated MAGP2. Deletion analysis of the C-terminal 20-amino acid domain that is defined by the PC cleavage site suggests that this domain also positively modulates matrix localization of MAGP2, in a manner that requires the amino-terminal half of the protein. Together, our data indicate that matrix localization of MAGP2 by its Matrix Binding Domain is promoted by PC cleavage and the presence of its C-terminal 20 amino acids.
authors.affiliation: Department of Biological Science, California State University, Fullerton, Fullerton, CA 92831, United States; Center for Applied Biotechnology Studies, California State University, Fullerton, Fullerton, CA 92831, United States. Electronic address: almiyamoto@fullerton.edu.
authors.forename: Alison
authors.initials: A
authors.lastname: Miyamoto
authors.affiliation: Department of Biological Science, California State University, Fullerton, Fullerton, CA 92831, United States; Center for Applied Biotechnology Studies, California State University, Fullerton, Fullerton, CA 92831, United States.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Donovan
authors.affiliation: Department of Biological Science, California State University, Fullerton, Fullerton, CA 92831, United States; Center for Applied Biotechnology Studies, California State University, Fullerton, Fullerton, CA 92831, United States.
authors.forename: Edgar
authors.initials: E
authors.lastname: Perez
authors.affiliation: Department of Biological Science, California State University, Fullerton, Fullerton, CA 92831, United States; Center for Applied Biotechnology Studies, California State University, Fullerton, Fullerton, CA 92831, United States.
authors.forename: Breanna
authors.initials: B
authors.lastname: Connett
authors.affiliation: Department of Biological Science, California State University, Fullerton, Fullerton, CA 92831, United States; Center for Applied Biotechnology Studies, California State University, Fullerton, Fullerton, CA 92831, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Cervantes
authors.affiliation: Department of Biological Science, California State University, Fullerton, Fullerton, CA 92831, United States; Center for Applied Biotechnology Studies, California State University, Fullerton, Fullerton, CA 92831, United States.
authors.forename: Khang
authors.initials: K
authors.lastname: Lai
authors.affiliation: Department of Biological Science, California State University, Fullerton, Fullerton, CA 92831, United States; Center for Applied Biotechnology Studies, California State University, Fullerton, Fullerton, CA 92831, United States.
authors.forename: Gordon
authors.initials: G
authors.lastname: Withers
authors.affiliation: Department of Biological Science, California State University, Fullerton, Fullerton, CA 92831, United States; Center for Applied Biotechnology Studies, California State University, Fullerton, Fullerton, CA 92831, United States.
authors.forename: Gregory
authors.initials: G
authors.lastname: Hogrebe
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003285:Contractile Proteins / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D000071840:Fibrillin-2; D000071837:Fibrillins; D007150:Immunohistochemistry; D051379:Mice; D020894:Microfibrils / Q000378:metabolism* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000378:metabolism*; D008854:Microscopy, Electron; D043484:Proprotein Convertases / Q000378:metabolism*; D000072260:RNA Splicing Factors
chemical_list: D003285:Contractile Proteins; D016326:Extracellular Matrix Proteins; C000605728:Fbn2 protein, mouse; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; D000072260:RNA Splicing Factors; C016598:microfibrillar protein; D043484:Proprotein Convertases
keywords: Fibrillin; MAGP2; MFAP5; Microfibril; Proprotein convertase