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Related Pathways Insulin Receptor Signaling PPAR alpha / RXR alpha Activation Hepatic Cholestasis View All Pathways

Synonyms: 4932439J01Rik, ALPHA SUBUNIT INSULIN RECEPTOR, CD220, D630014A15Rik, HHF5, INSR, INSULIN RECEPTOR, INSULIN RECEPTOR B, Insulin receptor beta, INSULIN RECEPTOR KINASE, INSULIN RPTK, IR, IR ALPHA, IR-B, IRK

Insulin Receptor Pathway

Insulin mediates cell signaling through activation with the insulin receptor (IR), a tyrosine kinase receptor. The activated IRkinase transduces the insulin signal by activating pathways such as the Ras-Raf-MEK-ERK, the PI3K-PDK-AKT, the c-Cbl-Glut4, the PI3K-Rab4-Glut4 and the PI3K-Rac-MEKK1-MKK4-JNK pathways. These pathways are modulated by complex networks of signaling inputs. The balancing of signals that transit the pathways stimulated by insulin provide the specific cell response to insulin signaling.

Insulin signaling is mediated by cascades of phosphorylation/ dephosphorylation events, guanine nucleotide exchange events and spatial positioning of signaling, scaffolding and adaptor molecules. Molecules that bind directly to the IR receptor such as the IRS family, SHC, PI3K and GRB10 transduce the insulin signal into the appropriate pathways.

Insulin stimulates the uptake of glucose primarily in adipocytes and myocytes by the translocation of the glucose channel, GLUT4, from the insulin responsive component (IRC) to the cell surface by two pathways, PI3K-AKT-atypical PKClamda-Rab4 and c-Cbl-APS-CAP. It modulates the growth/differentiation response via the Raf-MEK-ERK axis of the p21/Ras pathway. Protein synthesis, glycogenesis, lipogenesis and anti-apoptotic effects are controlled primarily via the PI3K-PDK-Akt/PKB pathway. The specific pathways require down-stream effectors such as GSK3, mTor, p70S6 kinase and pro-apoptotic factors Bad and FKHRL-1.