Monensin blocks the maturation of receptors for insulin and somatomedin C: identification of receptor precursors.
Cultured human lymphoid (IM-9) cells were labeled with [(35)S]methionine in the presence and absence of monensin, a carboxylic ionophore that inhibits post-translational protein maturation. Labeled receptors for insulin and somatomedin C were immunoprecipitated with antibodies specific for each receptor. Monensin inhibits the biosynthesis of mature alpha and beta subunits of both receptors and leads to the accumulation of immunoreactive polypeptides with molecular weights of 180,000. These 180,000 molecular weight polypeptides exist as disulfide-linked dimers and may be biosynthetic precursors of both alpha and beta subunits. In the presence of monensin, small amounts of immunoreactive polypeptides with molecular weights 115,000 and 89,000 also are produced. These may be abnormally processed forms of the alpha and beta subunits lacking residues normally added during terminal glycosylation. In cells treated with monensin, the polypeptides of molecular weights 180,000 and 115,000 can be affinity-labeled with (125)I-labeled insulin. These labeled polypeptides are immunoprecipitated by antibodies specific for insulin receptors but not by antibodies specific for somatomedin-C receptors. This indicates that the putative precursors for insulin and somatomedin-C receptors are distinct polypeptides, although they have similar molecular weights and similar modes of processing. A possible structural relationship between the precursors for these receptors and the type II insulin-like growth factor receptor is discussed.
D000818:Animals; D004220:Disulfides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005663:Furans / Q000494:pharmacology*; D008970:Molecular Weight; D008985:Monensin / Q000494:pharmacology*; D011498:Protein Precursors / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D011972:Receptor, Insulin / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D017451:Receptors, Somatomedin; D014357:Trypsin / Q000378:metabolism
D004220:Disulfides; D005663:Furans; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D008985:Monensin; D011972:Receptor, Insulin; D014357:Trypsin