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

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Abstract
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 .alpha. and .beta. subunits of both receptors and leads to the accumulation of immunoreactive polypeptides with MW of 180,000. These 180,000 MW 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 MW 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 MW 180,000 and 115,000 can be affinity-labeled with 124I-labeled insulin. These labeled polypeptides are immunoprecipitated by antibodies specific for insulin receptors but not by antibodies specific for somatomedin C receptors. The putative precursors for insulin and somatomedin C receptors apparently are distinct polypeptides, although they have similar MW 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.