Entry Name Insulin signaling pathway - Canis lupus familiaris (dog)
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 Canis lupus familiaris (dog) [GN:
cfa ]
Gene 100685147 PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X1 [KO:K04739 ]
100686806 SORBS1; sorbin and SH3 domain-containing protein 1 isoform X14 [KO:K06086 ]
100856379 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199 ]
403475 SREBF1; sterol regulatory element-binding protein 1 [KO:K07197 ]
403557 PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
403558 PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
403609 PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
403673 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
442949 SOCS3; suppressor of cytokine signaling 3 [KO:K04696 ]
474579 RHOQ; rho-related GTP-binding protein RhoQ [KO:K07194 ]
475545 RHEB; GTP-binding protein Rheb isoform X2 [KO:K07208 ]
475546 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
475590 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
475887 PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit isoform X1 [KO:K04739 ]
476726 TRIP10; cdc42-interacting protein 4 isoform X1 [KO:K07196 ]
477085 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
477263 PTPN1; tyrosine-protein phosphatase non-receptor type 1 isoform X12 [KO:K05696 ] [EC:3.1.3.48 ]
477766 PPP1R3C; protein phosphatase 1 regulatory subunit 3C isoform X1 [KO:K07189 ]
478139 PHKB; phosphorylase b kinase regulatory subunit beta isoform X2 [KO:K07190 ]
478351 CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183 ]
479127 PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X3 [KO:K07202 ]
479351 PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198 ] [EC:2.7.11.31 ]
479975 PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345 ] [EC:2.7.11.11 ]
480459 PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739 ]
480805 PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X2 [KO:K04739 ]
482411 PPP1R3A; protein phosphatase 1 regulatory subunit 3A isoform X5 [KO:K07189 ]
482509 MKNK1; MAP kinase-interacting serine/threonine-protein kinase 1 isoform X2 [KO:K04372 ] [EC:2.7.11.1 ]
482839 IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209 ] [EC:2.7.11.10 ]
482881 PPP1R3B; protein phosphatase 1 regulatory subunit 3B [KO:K07189 ]
483312 GRB2; growth factor receptor-bound protein 2 [KO:K04364 ]
483763 BAD; bcl2-associated agonist of cell death [KO:K02158 ]
484648 RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366 ] [EC:2.7.11.1 ]
485548 IRS2; insulin receptor substrate 2 isoform X8 [KO:K07187 ]
485953 PPP1R3D; protein phosphatase 1 regulatory subunit 3D [KO:K07189 ]
486295 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
486559 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
487235 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
487546 SHC4; SHC-transforming protein 4 isoform X2 [KO:K17449 ]
487870 EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259 ]
488084 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
488526 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200 ]
489099 EIF4E1B; eukaryotic translation initiation factor 4E type 1B isoform X1 [KO:K03259 ]
489571 PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X2 [KO:K07198 ] [EC:2.7.11.31 ]
489644 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922 ] [EC:2.7.1.153 ]
489784 PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871 ] [EC:2.7.11.19 ]
490006 SOCS1; suppressor of cytokine signaling 1 [KO:K04694 ]
490610 PPP1R3E; protein phosphatase 1 regulatory subunit 3E isoform X1 [KO:K07189 ]
490682 SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099 ]
491286 RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277 ]
491860 ELK1; ETS domain-containing protein Elk-1 [KO:K04375 ]
491877 PPP1R3F; protein phosphatase 1 regulatory subunit 3F isoform X2 [KO:K17453 ]
491956 PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X20 [KO:K07190 ]
607269 CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183 ]
607275 PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871 ] [EC:2.7.11.19 ]
608378 RPTOR; regulatory-associated protein of mTOR isoform X2 [KO:K07204 ]
609956 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
610238 EIF4E2; eukaryotic translation initiation factor 4E type 2 [KO:K03259 ]
611730 PDE3B; LOW QUALITY PROTEIN: cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X2 [KO:K13296 ] [EC:3.1.4.17 ]
611955 SHC2; SHC-transforming protein 2 isoform X2 [KO:K17447 ]
612212 MKNK2; MAP kinase-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K04372 ] [EC:2.7.11.1 ]
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 cfa04070 Phosphatidylinositol signaling system
KO pathway
