Entry Name Insulin signaling pathway - Zalophus californianus (California sea lion)
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 Zalophus californianus (California sea lion) [GN:
zca ]
Gene 113910547 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
113910938 PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739 ]
113911510 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
113911688 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
113913271 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199 ]
113916404 PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X1 [KO:K04739 ]
113917022 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113917179 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
113918898 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
113919807 EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259 ]
113920067 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
113921689 SORBS1; sorbin and SH3 domain-containing protein 1 isoform X39 [KO:K06086 ]
113921957 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
113923011 CALML3; LOW QUALITY PROTEIN: calmodulin-like protein 3 [KO:K02183 ]
113923834 PPP1R3C; protein phosphatase 1 regulatory subunit 3C isoform X1 [KO:K07189 ]
113924180 IKBKB; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209 ] [EC:2.7.11.10 ]
113924761 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113924866 EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259 ]
113924910 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
113925005 PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202 ]
113925301 PPP1R3B; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189 ]
113928514 EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259 ]
113928897 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
113929208 PRKAA1; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198 ] [EC:2.7.11.31 ]
113930574 PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190 ]
113930583 PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190 ]
113931145 PPP1R3F; protein phosphatase 1 regulatory subunit 3F isoform X1 [KO:K17453 ]
113932161 PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit isoform X1 [KO:K04739 ]
113934482 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199 ]
113935084 RAPGEF1; LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 1 [KO:K06277 ]
113936765 PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190 ]
113937116 RHOQ; rho-related GTP-binding protein RhoQ isoform X1 [KO:K07194 ]
113939022 RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204 ]
113939029 SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197 ]
113939382 PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit [KO:K04739 ]
113939579 GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364 ]
113939593 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 isoform X1 [KO:K07191 ]
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 zca04070 Phosphatidylinositol signaling system
KO pathway
