Human preproapolipoprotein C-II. Analysis of major plasma isoforms.
Apolipoprotein C-II plays a major role in lipid metabolism as a cofactor for lipoprotein lipase, the enzyme involved in the hydrolysis of triglyceride-rich lipoproteins. Apo-C-II is initially synthesized as a 101 amino acid protein that undergoes subsequent cotranslational cleavage of a signal peptide. Post-translational processing of apo-C-II has not been previously described. In this manuscript we identify four major plasma isoforms of apo-C-II by two-dimensional gel electrophoresis and immunoblot analysis that result from post-translational modification of apo-C-II. Neuraminidase studies have shown that two of these isoforms are early secreted sialic acid containing glycoproteins. Amino acid compositional and amino-terminal analysis have established that the major plasma isoform of apo-C-II is proapo-C-II. Proapo-C-II undergoes proteolytic cleavage of its amino-terminal hexapeptide to generate the mature form of apo-C-II. Thus, apo-C-II appears to be secreted as a carbohydrate containing proprotein that then undergoes deglycosylation and proteolytic cleavage to generate mature apo-C-II, a minor isoform in plasma. An improved understanding of the structural relationship of the various plasma isoforms of apo-C-II will help to elucidate the mechanisms involved in normal, as well as defective, processing of apo-C-II.
D000596:Amino Acids / Q000032:analysis; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000097:blood*; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007163:Immunosorbent Techniques; D008079:Lipoproteins, VLDL / Q000097:blood; D009439:Neuraminidase / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood*; D011499:Protein Processing, Post-Translational
D000596:Amino Acids; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D008079:Lipoproteins, VLDL; D011498:Protein Precursors; C048859:preproapolipoprotein C2; D009439:Neuraminidase