Entry Name Insulin signaling pathway - Macaca mulatta (rhesus 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 Macaca mulatta (rhesus monkey) [GN:
mcc ]
Gene 100423096 PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871 ] [EC:2.7.11.19 ]
100424331 SORBS1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086 ]
100425255 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
693753 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
694376 PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190 ]
695558 PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198 ] [EC:2.7.11.31 ]
695737 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
695770 PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739 ]
696146 SOCS4; suppressor of cytokine signaling 4 [KO:K04697 ]
696207 PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596 ] [EC:4.1.1.32 ]
697381 PPP1R3C; protein phosphatase 1 regulatory subunit 3C [KO:K07189 ]
698996 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
699128 PPP1R3B; protein phosphatase 1 regulatory subunit 3B [KO:K07189 ]
699764 PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190 ]
699806 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
700770 PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739 ]
701281 PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189 ]
702041 GRB2; growth factor receptor-bound protein 2 [KO:K04364 ]
702782 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X2 [KO:K07200 ]
703091 PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871 ] [EC:2.7.11.19 ]
703302 PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
703514 CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183 ]
703562 PPP1R3A; protein phosphatase 1 regulatory subunit 3A [KO:K07189 ]
703628 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
703732 EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259 ]
703934 TRIP10; cdc42-interacting protein 4 isoform X2 [KO:K07196 ]
705801 EXOC7; exocyst complex component 7 isoform X2 [KO:K07195 ]
706751 EIF4E; eukaryotic translation initiation factor 4E [KO:K03259 ]
706972 SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197 ]
707310 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
708981 PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739 ]
709298 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200 ]
709935 PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
709959 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
710061 MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X3 [KO:K04372 ] [EC:2.7.11.1 ]
710552 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
711180 SOCS1; suppressor of cytokine signaling 1 [KO:K04694 ]
712610 ELK1; ETS domain-containing protein Elk-1 [KO:K04375 ]
712848 RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204 ]
713209 PPP1R3E; protein phosphatase 1 regulatory subunit 3E [KO:K07189 ]
713487 EIF4E2; eukaryotic translation initiation factor 4E type 2 [KO:K03259 ]
713777 SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099 ]
714701 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
715272 RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277 ]
715680 SOCS3; suppressor of cytokine signaling 3 [KO:K04696 ]
715762 PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X3 [KO:K07202 ]
715772 SOCS2; suppressor of cytokine signaling 2 [KO:K04695 ]
715950 PPP1R3F; protein phosphatase 1 regulatory subunit 3F isoform X1 [KO:K17453 ]
716098 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
716390 PHKB; phosphorylase b kinase regulatory subunit beta [KO:K07190 ]
717740 BAD; bcl2-associated agonist of cell death [KO:K02158 ]
717769 RHOQ; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194 ]
718632 PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345 ] [EC:2.7.11.11 ]
719021 PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739 ]
719367 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
719508 INPP5A; type I inositol 1,4,5-trisphosphate 5-phosphatase isoform X1 [KO:K01106 ] [EC:3.1.3.56 ]
721735 PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
721821 MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369 ] [EC:2.7.12.2 ]
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 mcc04070 Phosphatidylinositol signaling system
KO pathway
