Signaling via the insulin-like growth factor-I receptor: Does it differ from insulin receptor signaling?

Vicky A. Blakesley, Angus Scrimgeour, Diana Esposito, Derek Le Roith

Research output: Contribution to journalShort surveypeer-review

157 Scopus citations

Abstract

The insulin and insulin-like growth factor (IGF-I) receptors while similar in structure and function serve different physiological functions in vivo. In non-disease states the insulin receptor is primarily involved in metabolic functions whereas the IGF-I receptor mediates growth and differentiation. The separation of these functions is controlled by a number of factors including the tissue distribution of the respective receptors. Modulation of the binding of the ligands insulin or IGF-I and IGF-II to their respective receptors by the local environment of the cell also offers signaling specificity mediated via the receptors. Each ligand binds to its respective receptor with high affinity. This high affinity binding is dictated by the primary sequence of both the ligand and the receptor. Furthermore IGF-binding proteins are specific for IGF-I and IGF-II thereby modulating the binding of the IGFs to the IGF-I receptor. In contrast insulin circulates unbound to any proteins and interacts in the free state with the insulin receptor. It has been postulated that downstream substrates of the activated receptors differ in their specificity for the receptors, thus lending further specificity to the actions mediated by the receptors. While a number of known endogenous substrates such as IRS-1, IRS-2 and Shc are utilized by both receptors, the structural differences in the β subunits of the two receptors has lead investigators to suggest that certain substrates may be unique to each receptor. Candidate substrates which show this specificity of action have been and are being described. Full eludication of the specificities of the insulin and IGF-I signaling pathways is of interest of course for a better understanding of intercellular communication. In addition, because the closely related proteins insulin and IGF-I are used clinically, a clear understanding of the pathways activated by these agents is essential if more specific therapeutic modalities are to be developed for use in disease states.

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalCytokine and Growth Factor Reviews
Volume7
Issue number2
DOIs
StatePublished - Aug 1996
Externally publishedYes

Keywords

  • IGF-1 receptor
  • Insulin receptor
  • Signaling

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