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Pathway Description
Insulin Signalling
Homo sapiens
Protein Pathway
Created: 2013-08-22
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
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Pubmed: 1397719
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Pubmed: 16625196
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Pubmed: 12690205
Capon DJ, Chen EY, Levinson AD, Seeburg PH, Goeddel DV: Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature. 1983 Mar 3;302(5903):33-7. doi: 10.1038/302033a0.
Pubmed: 6298635
Reddy EP: Nucleotide sequence analysis of the T24 human bladder carcinoma oncogene. Science. 1983 Jun 3;220(4601):1061-3. doi: 10.1126/science.6844927.
Pubmed: 6844927
Sekiya T, Fushimi M, Hori H, Hirohashi S, Nishimura S, Sugimura T: Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4771-5. doi: 10.1073/pnas.81.15.4771.
Pubmed: 6087347
Ebina Y, Ellis L, Jarnagin K, Edery M, Graf L, Clauser E, Ou JH, Masiarz F, Kan YW, Goldfine ID, et al.: The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. Cell. 1985 Apr;40(4):747-58. doi: 10.1016/0092-8674(85)90334-4.
Pubmed: 2859121
Ullrich A, Bell JR, Chen EY, Herrera R, Petruzzelli LM, Dull TJ, Gray A, Coussens L, Liao YC, Tsubokawa M, et al.: Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature. 1985 Feb 28-Mar 6;313(6005):756-61. doi: 10.1038/313756a0.
Pubmed: 2983222
Seino S, Seino M, Bell GI: Human insulin-receptor gene. Partial sequence and amplification of exons by polymerase chain reaction. Diabetes. 1990 Jan;39(1):123-8. doi: 10.2337/diacare.39.1.123.
Pubmed: 2210055
Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, Cohen P: Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr Biol. 1997 Apr 1;7(4):261-9. doi: 10.1016/s0960-9822(06)00122-9.
Pubmed: 9094314
Alessi DR, Deak M, Casamayor A, Caudwell FB, Morrice N, Norman DG, Gaffney P, Reese CB, MacDougall CN, Harbison D, Ashworth A, Bownes M: 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. Curr Biol. 1997 Oct 1;7(10):776-89. doi: 10.1016/s0960-9822(06)00336-8.
Pubmed: 9368760
Stephens L, Anderson K, Stokoe D, Erdjument-Bromage H, Painter GF, Holmes AB, Gaffney PR, Reese CB, McCormick F, Tempst P, Coadwell J, Hawkins PT: Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science. 1998 Jan 30;279(5351):710-4. doi: 10.1126/science.279.5351.710.
Pubmed: 9445477
Matsubara A, Wasson JC, Donelan SS, Welling CM, Glaser B, Permutt MA: Isolation and characterization of the human AKT1 gene, identification of 13 single nucleotide polymorphisms (SNPs), and their lack of association with Type II diabetes. Diabetologia. 2001 Jul;44(7):910-3. doi: 10.1007/s001250100577.
Pubmed: 11508278
Jones PF, Jakubowicz T, Pitossi FJ, Maurer F, Hemmings BA: Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4171-5. doi: 10.1073/pnas.88.10.4171.
Pubmed: 1851997
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
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