Role of the carboxyl-terminal domains of the insulin and insulin-like growth factor I receptors in receptor function

Teresa N. Faria, Vicky A. Blakesley, Hisanori Kato, Bethel Stannard, Derek LeRoith, Charles T. Roberts

    Research output: Contribution to journalArticle

    49 Scopus citations

    Abstract

    The insulin and insulin-like growth factor I receptors (IR and IGF-IR, respectively) are heterotetrameric tyrosine kinases consisting of two extracellular ligand-binding α subunits and two transmembrane catalytic β subunits. A number of lines of evidence have suggested that the IR and IGF- IR differ with respect to their ability to elicit mitogenic versus metabolic events upon activation by cognate ligands. To ascertain the contribution of the poorly conserved carboxyl-terminal domains to the differential functioning of the IR and IGF-IR, we have constructed receptor chimeras in which the carboxyl-terminal domain of one receptor was fused to the remainder of the heterologous receptor. The responses of a number of parameters after ligand stimulation were examined in stably transfected NIH-3T3 cells expressing the chimeric receptors or the analogous wild-type receptor sequence. Replacement of the IR carboxyl terminus with that of the IGF-IR severely affected insulin-stimulated responses, whereas substitution of the carboxyl terminus of the IGF-IR with that of the IR had a minimal effect. These data suggest that the carboxyl-terminal domains of the IR and IGF-IR are not interchangeable and that the mitogenic activity of the IR can be influenced by sequences present in the carboxyl-terminal domain. The analogous functions of the IGF-IR, on the other hand, do not appear to be greatly affected by the presence of the IR carboxyl-terminal domain.

    Original languageEnglish (US)
    Pages (from-to)13922-13928
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume269
    Issue number19
    StatePublished - May 13 1994

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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