Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Stat3 Signaling Pathway
Mus musculus
Category:
Protein Pathway
Sub-Categories:
Gene Regulatory
Cytokine Signaling
Cellular Response
Created: 2018-09-20
Last Updated: 2019-08-16
The STAT3 signalling pathway is a pathway activated by many different cytokines. It has also been found to be activated by many carcinogens. Cytokines are small proteins. These proteins are released by some of the cells in the immune system, and are vital to signalling pathways in the body of mammals. STAT3 is very important in the activation of the expression of certain mediators in the liver. STAT3 binds at the phosphotyrosine receptor which in turn phosphorylates tyrosine 705 at the C-terminal domain of STAT3, activating STAT3. If a receptor is missing tyrosine-kinase activity it will find tyrosine-kinases that are associated to the receptor, including JAK and Src when it is time for ligand engagement. Thanks to this recruitment, STAT3 is phosphorylated through the tyrosine phosphorylation cascade. This means that STAT3 is now activated, and its compounds disconnect from the receptor site, and relocate to the nucleus. Once there, the compounds bind to DNA response elements, and take part in many processes against target genes, such as apoptosis and cell proliferation, regulating their transcription.
References
Stat3 Signaling Pathway References
Zhong Z, Wen Z, Darnell JE Jr: Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994 Apr 1;264(5155):95-8. doi: 10.1126/science.8140422.
Pubmed: 8140422
Schaefer TS, Sanders LK, Nathans D: Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9097-101. doi: 10.1073/pnas.92.20.9097.
Pubmed: 7568080
Wen Z, Zhong Z, Darnell JE Jr: Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell. 1995 Jul 28;82(2):241-50. doi: 10.1016/0092-8674(95)90311-9.
Pubmed: 7543024
Karaghiosoff M, Neubauer H, Lassnig C, Kovarik P, Schindler H, Pircher H, McCoy B, Bogdan C, Decker T, Brem G, Pfeffer K, Muller M: Partial impairment of cytokine responses in Tyk2-deficient mice. Immunity. 2000 Oct;13(4):549-60.
Pubmed: 11070173
Argiriadi MA, Goedken ER, Banach D, Borhani DW, Burchat A, Dixon RW, Marcotte D, Overmeyer G, Pivorunas V, Sadhukhan R, Sousa S, Moore NS, Tomlinson M, Voss J, Wang L, Wishart N, Woller K, Talanian RV: Enabling structure-based drug design of Tyk2 through co-crystallization with a stabilizing aminoindazole inhibitor. BMC Struct Biol. 2012 Sep 20;12:22. doi: 10.1186/1472-6807-12-22.
Pubmed: 22995073
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
Yang X, Chung D, Cepko CL: Molecular cloning of the murine JAK1 protein tyrosine kinase and its expression in the mouse central nervous system. J Neurosci. 1993 Jul;13(7):3006-17.
Pubmed: 8331382
Wilks AF, Kurban RR, Hovens CM, Ralph SJ: The application of the polymerase chain reaction to cloning members of the protein tyrosine kinase family. Gene. 1989 Dec 21;85(1):67-74. doi: 10.1016/0378-1119(89)90465-4.
Pubmed: 2482828
Wilks AF: Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1603-7. doi: 10.1073/pnas.86.5.1603.
Pubmed: 2466296
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
Her JH, Wu J, Rall TB, Sturgill TW, Weber MJ: Sequence of pp42/MAP kinase, a serine/threonine kinase regulated by tyrosine phosphorylation. Nucleic Acids Res. 1991 Jul 11;19(13):3743. doi: 10.1093/nar/19.13.3743.
Pubmed: 1649458
ten Hoeve J, de Jesus Ibarra-Sanchez M, Fu Y, Zhu W, Tremblay M, David M, Shuai K: Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol. 2002 Aug;22(16):5662-8. doi: 10.1128/mcb.22.16.5662-5668.2002.
Pubmed: 12138178
Zhong Z, Wen Z, Darnell JE Jr: Stat3 and Stat4: members of the family of signal transducers and activators of transcription. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4806-10. doi: 10.1073/pnas.91.11.4806.
Pubmed: 7545930
Cirri P, Chiarugi P, Marra F, Raugei G, Camici G, Manao G, Ramponi G: c-Src activates both STAT1 and STAT3 in PDGF-stimulated NIH3T3 cells. Biochem Biophys Res Commun. 1997 Oct 20;239(2):493-7. doi: 10.1006/bbrc.1997.7493.
Pubmed: 9344858
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 SMP0067587
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