B RTK Receptor Family

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Ligand binding to RTK family receptors lead to dimerization of monomeric receptors or conformational changes in heterotetrameric receptors resulting in auto-phosphorylation of specific tyrosines in the cytoplasmic domain (Fig. 18). Tyro-sine autophosphorylation stimulates the intrinsic receptor tyrosine kinase activity and/or generates recruitment sites for downstream signaling proteins containing phosphotyrosine-recognition domains such as the Src homology 2 (SH2) or the phospho-tyrosine-binding (PTB) domain [84]. Efficient phosphorylation of the substrates by RTK also requires association of the substrate to the activated RTK. The PTB domain of insulin receptor substrate 1 (IRS1) binds at pTYR972 of activated IR, and the pleckstrin homology domain targets IRS-1 to

Figure 18 Schematic illustration of signaling cascades for the cellular responses to insulin-insulin receptor (IR) interactions. Insulin binding to its receptor activates tyrosine kinase activity resulting in autophosphorylation followed by binding of IR substrate (IRS), Shc, and STAT5b to specific PY residues of the receptor through SH2 domains. IRS-1 is a docking protein that induces various signaling pathways like MAPK through the Grb-2-SOS pathway, PI3 kinase, and Akt pathway. STAT5b binds to PY residues of IR and gets phosphorylated, followed by dimerization and translocation into the nucleus, where it induces gene expression.

Figure 18 Schematic illustration of signaling cascades for the cellular responses to insulin-insulin receptor (IR) interactions. Insulin binding to its receptor activates tyrosine kinase activity resulting in autophosphorylation followed by binding of IR substrate (IRS), Shc, and STAT5b to specific PY residues of the receptor through SH2 domains. IRS-1 is a docking protein that induces various signaling pathways like MAPK through the Grb-2-SOS pathway, PI3 kinase, and Akt pathway. STAT5b binds to PY residues of IR and gets phosphorylated, followed by dimerization and translocation into the nucleus, where it induces gene expression.

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