Essential role of tyrosine residues 1131, 1135, and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action

Hisanori Kato, Teresa N. Faria, Bethel Stannard, Charles Roberts, Derek LeRoith

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

The insulin and insulin-like growth factor-I (IGF-I) receptors are related heterotetramers consisting of two extracellular ligand-binding α-subunits and two transmembrane β-subunits whose cytoplasmic domains exhibit tyrosine kinase activity. Previous studies have shown that ATP binding by the cytoplasmic tyrosine kinase domains of these receptors is necessary to initiate the signal transduction pathway triggered by ligands or by ligand-mimetic antibodies, suggesting that receptor autophosphorylation is a necessary proximal step in this pathway. In the case of the insulin receptor, it has additionally been demonstrated that a cluster of three tyrosines in the kinase domain itself are the first to be phosphorylated, and that autophosphorylation of these particular residues is necessary for receptor activity. Using stably transfected NIH-3T3 cell lines, we now show that mutation of the analogous residues in the IGF-I receptor abolishes all short, intermediate, and long-term responses to IGF-I. These data suggest that the initial mechanisms of activation of the insulin and IGF-I receptors are very similar. Additionally, we have identified two parameters, induction of c-fos gene expression and ornithine decarboxylase enzyme activity, which are extremely sensitive to IGF-I stimulation and which will be particularly useful in evaluating the biological activity of other mutated versions of the IGF-I receptor.

Original languageEnglish (US)
Pages (from-to)40-50
Number of pages11
JournalMolecular Endocrinology
Volume8
Issue number1
StatePublished - Jan 1994
Externally publishedYes

Fingerprint

IGF Type 1 Receptor
Insulin-Like Growth Factor I
Tyrosine
Ligands
Protein-Tyrosine Kinases
Insulin
fos Genes
NIH 3T3 Cells
Ornithine Decarboxylase
Insulin Receptor
Receptor Protein-Tyrosine Kinases
Signal Transduction
Adenosine Triphosphate
Gene Expression
Cell Line
Mutation
Antibodies
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Essential role of tyrosine residues 1131, 1135, and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action. / Kato, Hisanori; Faria, Teresa N.; Stannard, Bethel; Roberts, Charles; LeRoith, Derek.

In: Molecular Endocrinology, Vol. 8, No. 1, 01.1994, p. 40-50.

Research output: Contribution to journalArticle

Kato, Hisanori ; Faria, Teresa N. ; Stannard, Bethel ; Roberts, Charles ; LeRoith, Derek. / Essential role of tyrosine residues 1131, 1135, and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action. In: Molecular Endocrinology. 1994 ; Vol. 8, No. 1. pp. 40-50.
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