Insulin/IGF-1 hybrid receptors: Implications for the dominant-negative phenotype in syndromes of insulin resistance

A. L. Frattali, J. L. Treadway, Jeffrey E. Pessin

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Classical insulin and IGF-1 receptors are α2β2 heterotetrameric complexes synthesized from two identical αβ half-receptor precursors. Recent data strongly suggests, however, that nonidentical αβ half-receptor precursors can assemble to generate hybrid holoreceptor species both in vivo and in vitro. This review focuses primarily on two types of hybrid receptors. The first type is an insulin/IGF-1 hybrid receptor generated by the association of an αβ insulin half-receptor with an αβ IGF-1 half-receptor. The second type is one formed from a wildtype (kinase-active) insulin or IGF-1 αβ half-receptor and a mutant (kinase-inactive) insulin αβ half-receptor. Although the functional properties of insulin/IGF-1 hybrid receptors have not yet been completely defined, wildtype/mutant hybrid receptors are essentially substrate kinase active. These data indicate that the mutant αβ half-receptor exerts a transdominant inhibition upon the wildtype αβ half-receptor within the α2β2 holoreceptor complex. This defect in substrate kinase activity may contribute to the molecular defect underlying some syndromes of severe insulin resistance and diabetes. Heterozygous individuals expressing both wildtype and mutant tyrosine kinase-defective insulin receptor precursors demonstrate varying degree of insulin resistance and diabetes. In addition, cell lines which express both endogenous wildtype and transfected kinase-defective insulin receptors display markedly decreased insulin and IGF-1 sensitivity and responsiveness. Formation of hybrid receptors which results in premature termination of insulin signal transduction may be one mechanism underlying the observation that kinase-inactive receptors inhibit the function of native receptors.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalJournal of Cellular Biochemistry
Volume48
Issue number1
StatePublished - 1992
Externally publishedYes

Fingerprint

IGF Type 1 Receptor
Insulin-Like Growth Factor I
Insulin Resistance
Phosphotransferases
Insulin
Phenotype
Insulin Receptor
Medical problems
Signal Transduction
Signal transduction
Defects
Cell Line
Substrates
Protein-Tyrosine Kinases
Cells
Association reactions

Keywords

  • Autophosphorylation
  • In vitro assembly
  • Insulin/IGF-1 hybrid receptors
  • Protein tyrosine kinase
  • Substrate phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Insulin/IGF-1 hybrid receptors : Implications for the dominant-negative phenotype in syndromes of insulin resistance. / Frattali, A. L.; Treadway, J. L.; Pessin, Jeffrey E.

In: Journal of Cellular Biochemistry, Vol. 48, No. 1, 1992, p. 43-50.

Research output: Contribution to journalArticle

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