Evidence for binding of human pregnancy zone protein-proteinase complex to alpha 2-macroglobulin receptors.
125I-labelled human pregnancy zone protein complexed with chymotrypsin was removed from the circulation with a half-time of 2.3 min after intravenous injection in rats. After 6 min about 67% of the label was present in the liver and about 3% was in the spleen, both in male and in female pregnant rats. The half-time of removal was more than 30 min for native pregnancy zone protein. Uptake into other organs, including placentae and feti, was negligible. 30 pM labelled pregnancy zone protein X chymotrypsin was specifically bound to rat hepatocytes and adipocytes and to human fibroblasts and monocyte-derived macrophages at 4 degrees C. Binding was almost completely abolished by a saturating concentration of unlabelled alpha 2-macroglobulin X trypsin. Binding of 15 pM labelled macroglobulin complex was completely abolished by a saturating concentration of pregnancy zone protein X chymotrypsin. In rat hepatocytes, binding of pregnancy zone protein complex was lower than that of alpha 2-macroglobulin complex at low ligand concentrations. Half-maximal receptor occupancy was obtained with about 300 pM pregnancy zone protein complex. Unlabelled alpha 2-macroglobulin or pregnancy zone protein complex failed to accelerate dissociation of the labelled pregnancy zone protein complex under conditions where dissociation of alpha 2-macroglobulin was markedly enhanced. It is concluded that pregnancy zone protein and alpha 2-macroglobulin complexes bind to the same receptors. The quantitative differences may be related to the fact that alpha 2-macroglobulin is a tetramer whereas the functional unit of pregnancy zone protein is probably a dimer.
D000818:Animals; D002918:Chymotrypsin / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*; D014018:Tissue Distribution; D014357:Trypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011257:Pregnancy Proteins; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D002918:Chymotrypsin; D014357:Trypsin