title: Comparison of the signaling abilities of the Drosophila and human insulin receptors in mammalian cells.
abstract: Chimeric receptors encoding either the whole or a portion of the cytoplasmic domain of the drosophila insulin receptor (IR) with the extracellular domain of the human IR were expressed either transiently in COS cells or stably in Chinese hamster ovary cells and compared with the wild-type human IR. All three receptors bound insulin equally and exhibited an insulin-activated tyrosine kinase activity. The ability of the drosophila cytoplasmic domain to mediate the tyrosine phosphorylation of insulin receptor substrate 1, stimulate cell proliferation, and activate MAP kinase was found to be indistinguishable from that of the human IR. The chimeric drosophila receptors did not bind more phosphatidylinositol 3-kinase than the human IR, despite containing a C-terminal extension with potential tyrosine phosphorylation sites in the motif recognized by the SH2 domain of this enzyme. Thus, the essential signal-transducing abilities of the IR appear to have been conserved from invertebrates to mammals, despite the considerable differences in the sequences of these receptors.
authors.affiliation: Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305, USA.
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: R
authors.initials: R
authors.lastname: Fernandez
authors.forename: R A
authors.initials: RA
authors.lastname: Roth
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary; D004331:Drosophila melanogaster / Q000737:chemistry*; D004789:Enzyme Activation; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011869:Radioligand Assay; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity
chemical_list: D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D011972:Receptor, Insulin