The IGF-I signaling pathway

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 sersine/threonine kinases that are ulitmately responsible for cell proliferation, modulation of tissue differentiation, and protection from apotosis. 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 transduction system in specific tissues. © 2007 Bentham Science Publishers Ltd.