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Pathway Description
Leucine Stimulation on Insulin Signaling
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Signaling
Created: 2018-08-31
Last Updated: 2019-08-16
The branched chain amino acid (BCAA) leucine is able to signal transduction pathways that modulate translation initiation for protein synthesis in skeleton muscles. In the presence of leucine, hyperphosphorylation of 4E-BP1 causes its affinity for eIF4E to be lowered. This allows eIF4F protein complexes to recognize, unfold and guide the mRNA to the 43S preinitiation complex thereby increasing translation initiation. In addition, leucine has a transient affect on the release of insulin and/or enhances sensitivity of muscle cells to insulin. A culmination of both signals at the mammalian target of rapamycin (mTOR) and perhaps other signaling, such as PKCδ, are needed for maximum translation initiation to occur.
References
Leucine Stimulation on Insulin Signaling References
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
Goldstein BJ, Dudley AL: The rat insulin receptor: primary structure and conservation of tissue-specific alternative messenger RNA splicing. Mol Endocrinol. 1990 Feb;4(2):235-44. doi: 10.1210/mend-4-2-235.
Pubmed: 2330003
Kasus-Jacobi A, Bereziat V, Perdereau D, Girard J, Burnol AF: Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2. Oncogene. 2000 Apr 13;19(16):2052-9. doi: 10.1038/sj.onc.1203469.
Pubmed: 10803466
Johansson GS, Arnqvist HJ: Insulin and IGF-I action on insulin receptors, IGF-I receptors, and hybrid insulin/IGF-I receptors in vascular smooth muscle cells. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1124-30. doi: 10.1152/ajpendo.00565.2005. Epub 2006 Jun 27.
Pubmed: 16803852
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
Sabers CJ, Martin MM, Brunn GJ, Williams JM, Dumont FJ, Wiederrecht G, Abraham RT: Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem. 1995 Jan 13;270(2):815-22. doi: 10.1074/jbc.270.2.815.
Pubmed: 7822316
Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH: RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell. 1994 Jul 15;78(1):35-43. doi: 10.1016/0092-8674(94)90570-3.
Pubmed: 7518356
Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM: RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1432-7. doi: 10.1073/pnas.95.4.1432.
Pubmed: 9465032
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 SMP0000682
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