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 alpha-subunits, containing hormone binding sites, and two membrane-spanning beta-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.
Laviola
Luigi
L
Department of Emergency and Organ Transplantation, Section on Internal Medicine, Endocrinology and Metabolic Diseases, University of Bari, Bari, Italy.
Natalicchio
Annalisa
A
Giorgino
Francesco
F
D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1