Monensin blocks the maturation of receptors for insulin and somatomedin C: Identification of receptor precursors

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RESUMO

Cultured human lymphoid (IM-9) cells were labeled with [35S]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 α and β 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 α and β 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 α and β 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 125I-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.

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