Monensin blocks the maturation of somatomedin C: Idetification. of -.r (receptor biosynthesis/receptor antibodies/insulin-like growth factors

Cultured human lymphoid (IM-9) cells were la- beled with (35S)methionine in the presence and absence of mo- nensin, a carboxylic ionophore that inhibits post-translational pro- tein maturation. Labeled receptors for insulin and somatomedin C were immunoprecipitated with antibodies specific for each re- ceptor. Monensin inhibits the biosynthesis of mature a and fi sub- units of both receptors and leads to the accumulation of immu- noreactive polypeptides with molecular weights of 180,000. These 180,000 molecular weight polypeptides exist as disulfide-linked di- mers and maybe biosynthetic precursors of both a and f3 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 a and f, subunits lacking residues normally added during terminal gly- cosylation. In cells treated with monensin, the polypeptides of mo- lecular weights 180,000 and 115,000 can be affinity-labeled with l2SI-labeled insulin. These labeled polypeptides are immunopre- cipitated by antibodies specific for insulin receptors but notbyan- tibodies 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 re- lationship between the precursors for these receptors and the type II insulin-like growth factor receptor is discussed.