title: Apolipoprotein C-II is a novel substrate for matrix metalloproteinases.
abstract: We previously reported an efficient proteomic approach to identify matrix metalloproteinase (MMP) substrates from complex protein mixture. Using the proteomic approach, apolipoprotein C-II (apoC-II), which is a cofactor of lipoprotein lipase (LPL) and a component of very-low density lipoprotein and chylomicron, has been identified as a putative MMP-14 substrate. Cleavage of apoC-II, with various MMPs, demonstrated that apoC-II is cleaved most efficiently by MMP-14, and also by MMP-7, among the tested MMPs. The 79-amino acid residue apoC-II was cleaved between Asn35 and Leu36 by MMP-14, and between Phe14 and Leu15 and between Asn35 and Leu36 by MMP-7. Cleavage of apoC-II by MMP-14 markedly decreased LPL activity and would thus impair hydrolysis of triglycerides in plasma and transfer of fatty acids to tissues. Our result suggests that cleavage of apoC-II by MMPs would be important for development of pathophysiological situations of apoC-II deficiency such as atherosclerosis.
authors.affiliation: Department of Biochemistry, College of Science, Protein Network Research Center, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Se Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Park
authors.forename: Seung-Taek
authors.initials: ST
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000378:metabolism*; D003001:Cloning, Molecular; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008969:Molecular Sequence Data; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
chemical_list: D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D020783:Matrix Metalloproteinase 7