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Insulin-like growth factors (IGFs) bind specifically to the IGF1 receptor on the cell surface of targeted tissues. 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. Activated receptor phosphorylates several substrates, including insulin receptor substrates (IRSs) and Src homology collagen (SHC). Phosphotyrosine residues in these substrates are recognized by certain Src homology 2 (SH2) domain-containing signaling molecules. 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). These bindings lead to the activation of downstream signaling pathways, PI 3-kinase pathway and Ras-mitogen-activated protein kinase (MAP kinase) pathway. 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. In this review, the well-established IGF1 receptor signaling pathways required for the induction of various bioactivities of IGFs are introduced. In addition, we will discuss how IGF signals are modulated by the other extracellular stimuli or by themselves based on our studies.
Authors : Hakuno Fumihiko , Takahashi Shin-Ichiro ,
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WP68: Androgen Receptor Signaling Pathway
WP252: Androgen Receptor Signaling Pathway
WP783: Androgen Receptor Signaling Pathway
WP1348: Androgen Receptor Signaling Pathway
WP908: B Cell Receptor Signaling Pathway
WP258: TGF-beta Receptor Signaling Pathway
WP1161: TGF-beta Receptor Signaling Pathway
WP1284: EPO Receptor Signaling
WP1354: B Cell Receptor Signaling Pathway
WP193: Signaling of Hepatocyte Growth Factor Receptor
WP1025: B Cell Receptor Signaling Pathway
WP1121: Kit Receptor Signaling Pathway
WP2328: Allograft rejection
WP1130: T Cell Receptor Signaling Pathway
WP949: Toll-like receptor signaling pathway
WP480: T Cell Receptor Signaling Pathway
WP794: B Cell Receptor Signaling Pathway
WP1341: Kit Receptor Signaling Pathway
WP894: T Cell Receptor Signaling Pathway
WP927: Signaling of Hepatocyte Growth Factor Receptor
WP285: B Cell Receptor Signaling Pathway
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP352: T Cell Receptor Signaling Pathway
WP1249: EPO Receptor Signaling
WP1374: Id Signaling Pathway
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