FactorsĪromatase activity and progesterone production Modulation of IGF signaling by other factors. Accordingly, to elucidate how IGF action is potentiated by other intercellular signaling molecules is essential for revealing IGF significance in target tissues. This mechanism is very important in order that IGF induces specific bioactivities in the right tissues at the right times. These findings suggest that IGFs act as permissive factors to augment the signals of other factors. IGFs predominantly mediate long-term action to determine the cell fates, whereas insulin mainly possesses metabolic activity.ĭespite the profuseness and diversity of these effects of IGFs, the in vitro biological effects of IGFs are relatively weak and often are not demonstrable except in the presence of other hormones or growth factors ( Table 1). On the other hand, insulin, whose structure is similar to IGFs, mediates anabolic biological activities, including increases in glucose and amino acid transport, induction of glycogen, lipid and protein syntheses and inhibition of gluconeogenesis, lipolysis and protein degradation. In many cell types, insulin-like growth factors (IGFs IGF1 and IGF2) have been shown to possess a variety of bioactivities, such as induction of growth or differentiation of target cells, cell survival and maintenance of cell function. In addition, we will discuss how IGF signals are modulated by the other extracellular stimuli or by themselves based on our studies. In this review, the well-established IGF1 receptor signaling pathways required for the induction of various bioactivities of IGFs are introduced. Activation of these signaling pathways is known to be required for the induction of various bioactivities of IGFs, including cell proliferation, cell differentiation and cell survival. These bindings lead to the activation of downstream signaling pathways, PI 3-kinase pathway and Ras-mitogen-activated protein kinase (MAP kinase) pathway. These include, for example, an 85 kDa regulatory subunit (p85) of phosphatidylinositol 3-kinase (PI 3-kinase), growth factor receptor-bound 2 (GRB2) and SH2-containing protein tyrosine phosphatase 2 (SHP2/Syp). Phosphotyrosine residues in these substrates are recognized by certain Src homology 2 (SH2) domain-containing signaling molecules. Activated receptor phosphorylates several substrates, including insulin receptor substrates (IRSs) and Src homology collagen (SHC). Ligand binding to the α subunit of the receptor leads to a conformational change in the β subunit, resulting in the activation of receptor tyrosine kinase activity.
Insulin-like growth factors (IGFs) bind specifically to the IGF1 receptor on the cell surface of targeted tissues.
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