A novel proteolytic activity in serum processes rat prohaptoglobin.
The heterotetrameric plasma glycoprotein rat haptoglobin previously was shown to be synthesized by hepatocytes in a precursor form, prohaptoglobin, which contains one alpha-subunit region and one beta-subunit region. Two of these molecules, each with a molecular weight of 45,000, are joined by a disulfide bond and subsequently the subunit regions of each polypeptide are separated by site-specific proteolysis, yielding the tetrameric native protein. Although some of this processing occurs intracellularly, a substantial proportion of the prohaptoglobin is secreted [J. M. Hanley, T. H. Haugen, and E. C. Heath (1983) J. Biol. Chem. 258, 7858-7869]. However, a proteolytic activity was found in rat plasma and serum which also is capable of site-specific cleavage of prohaptoglobin. Further investigation of this novel activity has demonstrated that it cleaves prohaptoglobin accurately, in the same site-specific manner as the intracellular protease, and that it most likely is not a serine protease or a metalloenzyme but can be inhibited by sulfhydryl-reactive compounds. Furthermore, it appears to be synthesized and secreted by hepatocytes, and thus may be identical to the intracellular processing protease.
D000470:Alkaloids / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002712:Chlorides; D002729:Chloromercuribenzoates / Q000494:pharmacology; D002848:Chromatography, DEAE-Cellulose; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006242:Haptoglobins / Q000096:biosynthesis / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008297:Male; D008985:Monensin / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000097:blood*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017026:Swainsonine; D013997:Time Factors; D014415:Tunicamycin / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology; D017967:Zinc Compounds; D020245:p-Chloromercuribenzoic Acid
D000470:Alkaloids; D002712:Chlorides; D002729:Chloromercuribenzoates; D006242:Haptoglobins; D011498:Protein Precursors; D017967:Zinc Compounds; C042034:prohaptoglobin; D014415:Tunicamycin; D020245:p-Chloromercuribenzoic Acid; C016837:zinc chloride; D008985:Monensin; D004492:Edetic Acid; D010447:Peptide Hydrolases; D015032:Zinc; D017026:Swainsonine