Entry Name Insulin signaling pathway - Rhinopithecus bieti (black snub-nosed monkey)
Description Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR.
Class Organismal Systems; Endocrine systemBRITE hierarchy
Pathway map Organism Rhinopithecus bieti (black snub-nosed monkey) [GN:
rbb ]
Gene 108512265 PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
108513587 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
108513945 RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277 ]
108514300 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
108514692 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
108517082 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
108518487 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200 ]
108521362 PPP1R3F; protein phosphatase 1 regulatory subunit 3F isoform X1 [KO:K17453 ]
108522034 PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190 ]
108523055 PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739 ]
108523111 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200 ]
108526071 PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202 ]
108526509 PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871 ] [EC:2.7.11.19 ]
108527015 PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739 ]
108530886 PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871 ] [EC:2.7.11.19 ]
108531858 EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259 ]
108532960 PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
108534006 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199 ]
108534276 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
108535636 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
108538244 EIF4E2; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 4E type 2 [KO:K03259 ]
108539355 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
108540485 PRKAR2B; LOW QUALITY PROTEIN: cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739 ]
108541175 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
108541574 IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446 ]
108542734 BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158 ]
108543529 PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739 ]
108543771 INPPL1; LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 [KO:K15909 ] [EC:3.1.3.86 ]
108543802 SORBS1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086 ]
108543920 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
108544591 PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
108544761 EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259 ]
Compound C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Ogawa W, Kasuga M.
Title [Mechanism of insulin action and diabetes mellitus]
Journal Seikagaku 75:1332-44 (2003)
Reference Authors Bevan P.
Title Insulin signalling.
Journal J Cell Sci 114:1429-30 (2001)
Reference Authors Kanzaki M, Pessin JE.
Title Insulin signaling: GLUT4 vesicles exit via the exocyst.
Journal Reference Authors Moodie SA, Alleman-Sposeto J, Gustafson TA.
Title Identification of the APS protein as a novel insulin receptor substrate.
Journal Reference Authors Gual P, Le Marchand-Brustel Y, Tanti JF.
Title Positive and negative regulation of insulin signaling through IRS-1 phosphorylation.
Journal Reference Authors Le Good JA, Ziegler WH, Parekh DB, Alessi DR, Cohen P, Parker PJ.
Title Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1.
Journal Reference Authors Saltiel AR, Kahn CR.
Title Insulin signalling and the regulation of glucose and lipid metabolism.
Journal Reference Authors Inoki K, Corradetti MN, Guan KL.
Title Dysregulation of the TSC-mTOR pathway in human disease.
Journal Reference Authors Ruggero D, Sonenberg N.
Title The Akt of translational control.
Journal Reference Authors Nave BT, Ouwens M, Withers DJ, Alessi DR, Shepherd PR.
Title Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation.
Journal Reference Authors Pullen N, Dennis PB, Andjelkovic M, Dufner A, Kozma SC, Hemmings BA, Thomas G.
Title Phosphorylation and activation of p70s6k by PDK1.
Journal Reference Authors Ogawa W, Matozaki T, Kasuga M.
Title Role of binding proteins to IRS-1 in insulin signalling.
Journal Mol Cell Biochem 182:13-22 (1998)
Reference Authors Ceresa BP, Pessin JE.
Title Insulin regulation of the Ras activation/inactivation cycle.
Journal Mol Cell Biochem 182:23-9 (1998)
Reference Authors Pollak MN, Schernhammer ES, Hankinson SE.
Title Insulin-like growth factors and neoplasia.
Journal Reference Authors Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME.
Title Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.
Journal Reference Authors Ferre P, Foufelle F
Title SREBP-1c transcription factor and lipid homeostasis: clinical perspective.
Journal Reference Authors Raghow R, Yellaturu C, Deng X, Park EA, Elam MB
Title SREBPs: the crossroads of physiological and pathological lipid homeostasis.
Journal Reference Authors Clement S, Krause U, Desmedt F, Tanti JF, Behrends J, Pesesse X, Sasaki T, Penninger J, Doherty M, Malaisse W, Dumont JE, Le Marchand-Brustel Y, Erneux C, Hue L, Schurmans S
Title The lipid phosphatase SHIP2 controls insulin sensitivity.
Journal Reference Authors Backers K, Blero D, Paternotte N, Zhang J, Erneux C
Title The termination of PI3K signalling by SHIP1 and SHIP2 inositol 5-phosphatases.
Journal Related rbb04070 Phosphatidylinositol signaling system
KO pathway
