Entry Name Insulin signaling pathway - Moschus berezovskii (Chinese forest musk deer)
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 Moschus berezovskii (Chinese forest musk deer) [GN:
mbez ]
Gene 129534873 PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190 ]
129534886 PPP1R3F; protein phosphatase 1 regulatory subunit 3F isoform X1 [KO:K17453 ]
129535225 PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190 ]
129536744 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
129537811 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200 ]
129537884 EIF4E2; eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259 ]
129539680 RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277 ]
129540801 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
129541115 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
129542622 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
129542678 SLC2A4; solute carrier family 2, facilitated glucose transporter member 4 [KO:K07191 ]
129544226 SREBF1; sterol regulatory element-binding protein 1 isoform X1 [KO:K07197 ]
129544632 RPTOR; LOW QUALITY PROTEIN: regulatory-associated protein of mTOR [KO:K07204 ]
129544780 PRKAR1A; cAMP-dependent protein kinase type I-alpha regulatory subunit isoform X1 [KO:K04739 ]
129545814 PRKAR1B; cAMP-dependent protein kinase type I-beta regulatory subunit [KO:K04739 ]
129547131 PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190 ]
129547146 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
129547817 PRKAR2A; cAMP-dependent protein kinase type II-alpha regulatory subunit [KO:K04739 ]
129548700 PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
129549364 PPP1R3B; protein phosphatase 1 regulatory subunit 3B isoform X1 [KO:K07189 ]
129549398 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
129550970 CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183 ]
129551508 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
129552397 PRKAR2B; cAMP-dependent protein kinase type II-beta regulatory subunit [KO:K04739 ]
129552799 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200 ]
129553207 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
129555516 SORBS1; sorbin and SH3 domain-containing protein 1 isoform X1 [KO:K06086 ]
129558881 EIF4E1B; eukaryotic translation initiation factor 4E type 1B [KO:K03259 ]
129559156 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
129561477 PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202 ]
129561564 EIF4E; eukaryotic translation initiation factor 4E isoform X1 [KO:K03259 ]
129562982 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
129564117 IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446 ]
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 mbez04070 Phosphatidylinositol signaling system
KO pathway
