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Pathway Description
Insulin Signalling
Rattus norvegicus
Category:
Protein Pathway
Sub-Categories:
Gene Regulatory
Kinase Signaling
Cellular Response
Created: 2018-08-31
Last Updated: 2019-08-16
Insulin is responsible for the regulation of glucose levels in the body. It stimulates the storage of energy and inhibits the breakdown of high energy metabolites. Glycogen and lipid biosynthesis are upregulated, and conversely, glycogen and fatty acid metabolism are down-regulated. Insulin also modulates transcription and translation. Binding of insulin to the insulin receptor (IR) results in the activation of its tyrosine kinase activity leading to IR autophosphorylation. IR then phosphorylates several substrates that lead to the activation of an intracellular signalling cascade. IR activation leads to the activation of H-Ras, MAPK1-3, and PI3-kinase pathways. The activation of these pathways leads to modulation of key proteins in glycogen metabolism/lipid metabolism and transcription/translation.
References
Insulin Signalling References
Tannert A, Voigt P, Burgold S, Tannert S, Schaefer M: Signal amplification between Gbetagamma release and PI3Kgamma-mediated PI(3,4,5)P3 formation monitored by a fluorescent Gbetagamma biosensor protein and repetitive two component total internal reflection/fluorescence redistribution after photobleaching analysis. Biochemistry. 2008 Oct 28;47(43):11239-50. doi: 10.1021/bi800596b. Epub 2008 Oct 2.
Pubmed: 18831540
Sun XJ, Rothenberg P, Kahn CR, Backer JM, Araki E, Wilden PA, Cahill DA, Goldstein BJ, White MF: Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature. 1991 Jul 4;352(6330):73-7. doi: 10.1038/352073a0.
Pubmed: 1648180
Rothenberg PL, Lane WS, Karasik A, Backer J, White M, Kahn CR: Purification and partial sequence analysis of pp185, the major cellular substrate of the insulin receptor tyrosine kinase. J Biol Chem. 1991 May 5;266(13):8302-11.
Pubmed: 2022647
Backer JM, Myers MG Jr, Shoelson SE, Chin DJ, Sun XJ, Miralpeix M, Hu P, Margolis B, Skolnik EY, Schlessinger J, et al.: Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation. EMBO J. 1992 Sep;11(9):3469-79.
Pubmed: 1380456
Ruta M, Wolford R, Dhar R, Defeo-Jones D, Ellis RW, Scolnick EM: Nucleotide sequence of the two rat cellular rasH genes. Mol Cell Biol. 1986 May;6(5):1706-10. doi: 10.1128/mcb.6.5.1706.
Pubmed: 3023901
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Damante G, Filetti S, Rapoport B: Nucleotide sequence and characterization of the 5' flanking region of the rat Ha-ras protooncogene. Proc Natl Acad Sci U S A. 1987 Feb;84(3):774-8. doi: 10.1073/pnas.84.3.774.
Pubmed: 3027702
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000391
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