Posttranslational processing of human alpha 2-HS glycoprotein (human fetuin). Evidence for the production of a phosphorylated single-chain form by hepatoma cells.
alpha 2-HS glycoprotein (alpha 2-HS) is a major protein occurring in human blood and calciferous tissues. Due to extensive sequence identity, alpha 2-HS has been grouped with the fetuins, a family of proteins that occur in fetal plasma in high concentrations. Native alpha 2-HS undergoes a series of posttranslational modifications including proteolytic processing, multiple N-glycosylations and O-glycosylations, and sulfation of the carbohydrate side chains. Various two-chain forms of alpha 2-HS have been prepared from human plasma, however, the single-chain precursor has not yet been isolated. Here, we have studied the biosynthesis of alpha 2-HS by a human hepatoma cell line, HepG2. We demonstrate that a single-chain form and the two-chain form of alpha 2-HS are secreted by this cell line. The alpha 2-HS forms are further modified by phosphorylation on multiple serine residues. Mapping studies indicate that the connecting peptide region releasable from the heavy chain of alpha 2-HS contains at least one such phosphorylation site. Our results identify proteolytic trimming and/or phosphorylation as modifications possibly regulating the biological effects of alpha 2-HS and the homologous fetuins.
Jahnen-Dechent
W
W
Institut für Physiologische Chemie und Pathobiochemie, Universität Mainz, Germany.
Trindl
A
A
Godovac-Zimmermann
J
J
Müller-Esterl
W
W
D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000378:metabolism*
D000509:alpha-Fetoproteins