Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
FAS signaling pathway ( CD95 )
Mus musculus
Category:
Protein Pathway
Sub-Categories:
Immunological
Apoptosis Signaling
Kinase Signaling
Cellular Response
Created: 2018-09-20
Last Updated: 2019-08-16
Fas ligand is a transmembrane protein part of the tumor necrosis factor (TNF) family. It plays a role in inducing apoptosis and is an important regulator of the immune system. Fas ligand signals through the Fas receptor on target cells. Fas ligand binds to the receptor and forms the death-inducing signalling complex, including the Fas-associated death domain, death-domain associated protein, and caspase-10. Caspases are synthesized as inactive pro-caspases. Caspases are are proteases that cleave their substrates. Caspase-8 is an initiator caspase that is activated in response to pro-apoptotic stimulus and causes a cascade of further caspase activity by cleaving and activating effector caspases, like caspases -3 and -7. Once activated, caspases -3 and -7 cleave downstream proteins. Caspase-8 activity is regulated by CASP8 and FADD-like apoptosis regulator. Kinases activate mitogen-activated protein kinases which activate pro-apoptotic JNK activity.
References
FAS signaling pathway ( CD95 ) References
Takahashi T, Tanaka M, Brannan CI, Jenkins NA, Copeland NG, Suda T, Nagata S: Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 1994 Mar 25;76(6):969-76. doi: 10.1016/0092-8674(94)90375-1.
Pubmed: 7511063
Peitsch MC, Tschopp J: Comparative molecular modelling of the Fas-ligand and other members of the TNF family. Mol Immunol. 1995 Jul;32(10):761-72. doi: 10.1016/0161-5890(95)00016-8.
Pubmed: 7544870
Lynch DH, Watson ML, Alderson MR, Baum PR, Miller RE, Tough T, Gibson M, Davis-Smith T, Smith CA, Hunter K, et al.: The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster. Immunity. 1994 May;1(2):131-6.
Pubmed: 7889405
Watanabe-Fukunaga R, Brannan CI, Itoh N, Yonehara S, Copeland NG, Jenkins NA, Nagata S: The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol. 1992 Feb 15;148(4):1274-9.
Pubmed: 1371136
Villa-Morales M, Santos J, Perez-Gomez E, Quintanilla M, Fernandez-Piqueras J: A role for the Fas/FasL system in modulating genetic susceptibility to T-cell lymphoblastic lymphomas. Cancer Res. 2007 Jun 1;67(11):5107-16. doi: 10.1158/0008-5472.CAN-06-4006.
Pubmed: 17545588
Adachi M, Watanabe-Fukunaga R, Nagata S: Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1756-60. doi: 10.1073/pnas.90.5.1756.
Pubmed: 7680478
Chu K, Niu X, Williams LT: A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11894-8. doi: 10.1073/pnas.92.25.11894.
Pubmed: 8524870
Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M, Hlavina W, Kapustin Y, Meric P, Maglott D, Birtle Z, Marques AC, Graves T, Zhou S, Teague B, Potamousis K, Churas C, Place M, Herschleb J, Runnheim R, Forrest D, Amos-Landgraf J, Schwartz DC, Cheng Z, Lindblad-Toh K, Eichler EE, Ponting CP: Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 2009 May 5;7(5):e1000112. doi: 10.1371/journal.pbio.1000112. Epub 2009 May 26.
Pubmed: 19468303
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
Zhang J, Winoto A: A mouse Fas-associated protein with homology to the human Mort1/FADD protein is essential for Fas-induced apoptosis. Mol Cell Biol. 1996 Jun;16(6):2756-63. doi: 10.1128/mcb.16.6.2756.
Pubmed: 8649383
Hsu H, Shu HB, Pan MG, Goeddel DV: TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell. 1996 Jan 26;84(2):299-308. doi: 10.1016/s0092-8674(00)80984-8.
Pubmed: 8565075
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y: The transcriptional landscape of the mammalian genome. Science. 2005 Sep 2;309(5740):1559-63. doi: 10.1126/science.1112014.
Pubmed: 16141072
Sakamaki K, Tsukumo S, Yonehara S: Molecular cloning and characterization of mouse caspase-8. Eur J Biochem. 1998 Apr 15;253(2):399-405. doi: 10.1046/j.1432-1327.1998.2530399.x.
Pubmed: 9654089
Van de Craen M, Van Loo G, Declercq W, Schotte P, Van den brande I, Mandruzzato S, van der Bruggen P, Fiers W, Vandenabeele P: Molecular cloning and identification of murine caspase-8. J Mol Biol. 1998 Dec 11;284(4):1017-26. doi: 10.1006/jmbi.1998.2226.
Pubmed: 9837723
Yang X, Khosravi-Far R, Chang HY, Baltimore D: Daxx, a novel Fas-binding protein that activates JNK and apoptosis. Cell. 1997 Jun 27;89(7):1067-76. doi: 10.1016/s0092-8674(00)80294-9.
Pubmed: 9215629
Zhong S, Salomoni P, Ronchetti S, Guo A, Ruggero D, Pandolfi PP: Promyelocytic leukemia protein (PML) and Daxx participate in a novel nuclear pathway for apoptosis. J Exp Med. 2000 Feb 21;191(4):631-40. doi: 10.1084/jem.191.4.631.
Pubmed: 10684855
Ecsedy JA, Michaelson JS, Leder P: Homeodomain-interacting protein kinase 1 modulates Daxx localization, phosphorylation, and transcriptional activity. Mol Cell Biol. 2003 Feb;23(3):950-60. doi: 10.1128/mcb.23.3.950-960.2003.
Pubmed: 12529400
Goltsev YV, Kovalenko AV, Arnold E, Varfolomeev EE, Brodianskii VM, Wallach D: CASH, a novel caspase homologue with death effector domains. J Biol Chem. 1997 Aug 8;272(32):19641-4. doi: 10.1074/jbc.272.32.19641.
Pubmed: 9289491
Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J: Inhibition of death receptor signals by cellular FLIP. Nature. 1997 Jul 10;388(6638):190-5. doi: 10.1038/40657.
Pubmed: 9217161
Chin AI, Dempsey PW, Bruhn K, Miller JF, Xu Y, Cheng G: Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Nature. 2002 Mar 14;416(6877):190-4. doi: 10.1038/416190a.
Pubmed: 11894097
Park JH, Kim YG, McDonald C, Kanneganti TD, Hasegawa M, Body-Malapel M, Inohara N, Nunez G: RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. J Immunol. 2007 Feb 15;178(4):2380-6. doi: 10.4049/jimmunol.178.4.2380.
Pubmed: 17277144
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 SMP0069695
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