Abstract
The insulin-like growth factor (IGF)-I is implicated in the regulation of protein turnover and exerts potent mitogenic and differentiating effects on most cell types. IGF-I biological actions are mediated by the IGF-I receptor, comprised of two extra-cellular α-subunits, containing hormone binding sites, and two membrane-spanning β-subunits, encoding an intracellular tyrosine kinase. Hormone binding activates the receptor kinase, leading to receptor autophosphorylation and tyrosine phosphorylation of multiple substrates, including the IRS and Shc proteins. Through these initial tyrosine phosphorylation reactions, IGF-I signals are transduced to a complex network of intracellular lipid and serine/ threonine kinases that are ultimately responsible for cell proliferation, modulation of tissue differentiation, and protection from apoptosis. This review will focus on the IGF-I receptor structure and function, its intracellular signaling pathways, and some important implications of the activation of the IGF-I signal transduction system in specific tissues.
Keywords: IGF-I receptor, insulin receptor, PI 3-kinase, Akt, ERK
Current Pharmaceutical Design
Title: The IGF-I Signaling Pathway
Volume: 13 Issue: 7
Author(s): Luigi Laviola, Annalisa Natalicchio and Francesco Giorgino
Affiliation:
Keywords: IGF-I receptor, insulin receptor, PI 3-kinase, Akt, ERK
Abstract: The insulin-like growth factor (IGF)-I is implicated in the regulation of protein turnover and exerts potent mitogenic and differentiating effects on most cell types. IGF-I biological actions are mediated by the IGF-I receptor, comprised of two extra-cellular α-subunits, containing hormone binding sites, and two membrane-spanning β-subunits, encoding an intracellular tyrosine kinase. Hormone binding activates the receptor kinase, leading to receptor autophosphorylation and tyrosine phosphorylation of multiple substrates, including the IRS and Shc proteins. Through these initial tyrosine phosphorylation reactions, IGF-I signals are transduced to a complex network of intracellular lipid and serine/ threonine kinases that are ultimately responsible for cell proliferation, modulation of tissue differentiation, and protection from apoptosis. This review will focus on the IGF-I receptor structure and function, its intracellular signaling pathways, and some important implications of the activation of the IGF-I signal transduction system in specific tissues.
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Cite this article as:
Laviola Luigi, Natalicchio Annalisa and Giorgino Francesco, The IGF-I Signaling Pathway, Current Pharmaceutical Design 2007; 13 (7) . https://dx.doi.org/10.2174/138161207780249146
DOI https://dx.doi.org/10.2174/138161207780249146 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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