
Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Ras Signaling Pathway
Rattus norvegicus
Category:
Protein Pathway
Sub-Categories:
Gene Regulatory
Kinase Signaling
Apoptosis Signaling
Cellular Response
Created: 2018-08-31
Last Updated: 2019-09-13
RAS signalling pathway is one of the main pathways to transduce intracellular signals in response to mitogens to controls cell growth, survival and anti-apoptotic programs. RAS proteins are GTP-binding proteins and must be bound to GTP to be active. Active RAS binds and activates effector enzymes that control cell proliferation, survival and other cell behaviours. RAS interacts directly with the catalytic subunit of PI3K to activate lipid kinases controlling the activity of downstream enzymes. Some of these kinases have anti-apoptotic activity, playing an important role in the survival signal of RAS. PI3K is also involved in the regulation of the actin cytoskeleton and transcription factor pathways. RAS also effects exchange factors causing inhibition of transcription factors from FoxO family, part of promoting cell cycle arrest and apoptosis. Normal function of these proteins require post-transcriptional modification. Pathway mutations in activation may result in human tumours.
References
Ras Signaling Pathway References
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
Albright CF, Giddings BW, Liu J, Vito M, Weinberg RA: Characterization of a guanine nucleotide dissociation stimulator for a ras-related GTPase. EMBO J. 1993 Jan;12(1):339-47.
Pubmed: 8094051
Huang L, Weng X, Hofer F, Martin GS, Kim SH: Three-dimensional structure of the Ras-interacting domain of RalGDS. Nat Struct Biol. 1997 Aug;4(8):609-15.
Pubmed: 9253406
Wildey GM, Viggeswarapu M, Rim S, Denker JK: Isolation of cDNA clones and tissue expression of rat ral A and ral B GTP-binding proteins. Biochem Biophys Res Commun. 1993 Jul 15;194(1):552-9. doi: 10.1006/bbrc.1993.1855.
Pubmed: 7687439
Cantor SB, Urano T, Feig LA: Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases. Mol Cell Biol. 1995 Aug;15(8):4578-84. doi: 10.1128/mcb.15.8.4578.
Pubmed: 7623849
Quaroni A, Paul EC: Cytocentrin is a Ral-binding protein involved in the assembly and function of the mitotic apparatus. J Cell Sci. 1999 Mar;112 ( Pt 5):707-18.
Pubmed: 9973605
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.
Pubmed: 22673903
Han JS, Kim JH, Kim JG, Park JB, Noh DY, Lee KH: Molecular cloning and sequencing of rat Cdc42 GTPase cDNA. Exp Mol Med. 2000 Sep 30;32(3):115-9. doi: 10.1038/emm.2000.20.
Pubmed: 11048641
Murakoshi H, Wang H, Yasuda R: Local, persistent activation of Rho GTPases during plasticity of single dendritic spines. Nature. 2011 Apr 7;472(7341):100-4. doi: 10.1038/nature09823. Epub 2011 Mar 20.
Pubmed: 21423166
Sun Y, Buki KG, Ettala O, Vaaraniemi JP, Vaananen HK: Possible role of direct Rac1-Rab7 interaction in ruffled border formation of osteoclasts. J Biol Chem. 2005 Sep 16;280(37):32356-61. doi: 10.1074/jbc.M414213200. Epub 2005 Jul 21.
Pubmed: 16040606
Shibata S, Nagase M, Yoshida S, Kawarazaki W, Kurihara H, Tanaka H, Miyoshi J, Takai Y, Fujita T: Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nat Med. 2008 Dec;14(12):1370-6. doi: 10.1038/nm.1879. Epub 2008 Nov 23.
Pubmed: 19029984
Li X, Lee AY: Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through RhoGDIalpha-mediated inactivation of Rac1 GTPase. J Biol Chem. 2010 Oct 15;285(42):32436-45. doi: 10.1074/jbc.M110.120451. Epub 2010 Aug 9.
Pubmed: 20696765
Heron-Milhavet L, Khouya N, Fernandez A, Lamb NJ: Akt1 and Akt2: differentiating the aktion. Histol Histopathol. 2011 May;26(5):651-62. doi: 10.14670/HH-26.651.
Pubmed: 21432781
Konishi H, Shinomura T, Kuroda S, Ono Y, Kikkawa U: Molecular cloning of rat RAC protein kinase alpha and beta and their association with protein kinase C zeta. Biochem Biophys Res Commun. 1994 Nov 30;205(1):817-25. doi: 10.1006/bbrc.1994.2738.
Pubmed: 7999118
Kitamura T, Ogawa W, Sakaue H, Hino Y, Kuroda S, Takata M, Matsumoto M, Maeda T, Konishi H, Kikkawa U, Kasuga M: Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport. Mol Cell Biol. 1998 Jul;18(7):3708-17. doi: 10.1128/mcb.18.7.3708.
Pubmed: 9632753
Song JS, Haleem-Smith H, Arudchandran R, Gomez J, Scott PM, Mill JF, Tan TH, Rivera J: Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway. J Immunol. 1999 Jul 15;163(2):802-10.
Pubmed: 10395673
D'Agata V, Magro G, Travali S, Musco S, Cavallaro S: Cloning and expression of the programmed cell death regulator Bad in the rat brain. Neurosci Lett. 1998 Feb 27;243(1-3):137-40. doi: 10.1016/s0304-3940(98)00116-5.
Pubmed: 9535132
Hsu SY, Kaipia A, Zhu L, Hsueh AJ: Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11. Mol Endocrinol. 1997 Nov;11(12):1858-67. doi: 10.1210/mend.11.12.0023.
Pubmed: 9369453
Hamner S, Arumae U, Li-Ying Y, Sun YF, Saarma M, Lindholm D: Functional characterization of two splice variants of rat bad and their interaction with Bcl-w in sympathetic neurons. Mol Cell Neurosci. 2001 Jan;17(1):97-106. doi: 10.1006/mcne.2000.0905.
Pubmed: 11161472
Yakovlev AG, Ota K, Wang G, Movsesyan V, Bao WL, Yoshihara K, Faden AI: Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury. J Neurosci. 2001 Oct 1;21(19):7439-46.
Pubmed: 11567033
Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F: Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493-521. doi: 10.1038/nature02426.
Pubmed: 15057822
Nam YJ, Mani K, Ashton AW, Peng CF, Krishnamurthy B, Hayakawa Y, Lee P, Korsmeyer SJ, Kitsis RN: Inhibition of both the extrinsic and intrinsic death pathways through nonhomotypic death-fold interactions. Mol Cell. 2004 Sep 24;15(6):901-12. doi: 10.1016/j.molcel.2004.08.020.
Pubmed: 15383280
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 SMP0063784
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings