Amino acid sequences Gly-Pro-Leu-Tyr and Asn-Pro-Glu-Tyr in the submembranous domain of the insulin receptor are required for normal endocytosis.

摘要: We have recently shown that the immediately submembranous domain of human insulin receptor (hIR) is required for rapid ligand-dependent internalization (Thies, R. S., Webster, N. J., and McClain, D. A. (1990) J. Biol. Chem. 265, 10132-10137). This region contains one copy an NPXY sequence endocytosis low density lipoprotein receptor. In order to dissect analyze specific sequences involved in receptor, we mutated from NPEY (residues 957-960) APEA (NPEY/APEA). addition, a similar same region, changing GPLY 950-953) APLA (GPLY/APLA). The cDNAs encoding normal hIR these mutant receptors were transfected into Rat 1 fibroblasts. expressed bound with high affinity retained insulin-stimulated tyrosine kinase activity. Despite ability bind undergo autophosphorylation, GPLY/APLA internalized at only 32% rate occupancy. On other hand, NPEY/APEA 87% rate. These results confirmed by measuring photoaffinity-labeled receptors. Another both mutations lesser degree than equivalent seen entire deleted. A complete but C-terminal deleted exhibited basal conclude information contained and, extent, are necessary not sufficient signaling