Single tyrosine substitution in the insulin-like growth factor i receptor inhibits ligand-induced receptor autophosphorylation and internalization, but not mitogenesis

Bethel Stannard, Vicky Blakesley, Hisanori Kato, Charles T. Roberts, Derek Leroith

    Research output: Contribution to journalArticle

    17 Scopus citations

    Abstract

    The tyrosine kinase domains of the insulin and insulin-like growth factor I (IGF-I) receptors play an essential role in signal transduction. After ligand binding, these receptors undergo autophosphorylation, with a cluster of three tyrosines (residues 1131, 1135, and 1136 in the IGF-I receptor) being the first to be phosphorylated. Mutation of the ATP-binding site or substitution of this triple tyrosine cluster in the catalytic domain blocks essentially all of the functions of these receptors. Using stably transfected NIH-3T3 cell lines, we studied the effect of a mutation of tyrosine 1131 of the triple tyrosine cluster of the IGF-I receptor to phenylalanine. This mutation significantly reduced IGF-I-induced β-subunit autophosphorylation, whereas phosphorylation of the endogenous substrate IRS-1 was unaffected. Despite the reduction in autophosphorylation and receptor internalization, IGF-I-induced thymidine incorporation and cellular proliferation were unaffected. Thus, the extent of receptor autophosphorylation and internalization does not appear to be a limiting factor for IGF-I-stimulated mitogenesis.

    Original languageEnglish (US)
    Pages (from-to)4918-4924
    Number of pages7
    JournalEndocrinology
    Volume136
    Issue number11
    DOIs
    StatePublished - Nov 1995

    ASJC Scopus subject areas

    • Endocrinology

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