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.
|Number of pages||8|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2006 Jan 6|
Bibliographical noteFunding Information:
We thank Dr. Gregory I. Goldberg (Washington University School of Medicine, St. Louis, USA) for pBS-MMP-9 and Dr. Min-Young Kim (AngioLab, Taejon, Republic of Korea) for pBacPAK9-MMP-3. We thank Ms. Seung Hwa Yun for preparation of MMP-7. This work was supported by grants from the Ministry of Science and Technology of Korea and the Korea Science and Engineering Foundation through the project for Studies on Ubiquitome Functions, the National Research Laboratory program, and the Protein Network Research Center at Yonsei University, as well as from the Ministry of Education of Korea through the Brain Korea 21 project.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology