Tyrosine-Protein Kinase JAK2 (JAK2) Human Recombinant Protein

Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.

Cloning and characterization of human Jak-2 kinase high mRNA expression in immune cells and muscle tissue.Saltzman A., Stone M., Franks C., Searfoss G., Munro R., Jaye M., Ivashchenko Y.Biochem. Biophys. Res. Commun. 246:627-633(1998) Cloning and characterization of the human homolog of mouse Jak2.Dalal I., Arpaia E., Dadi H., Kulkarni S., Squire J., Roifman C.M.Blood 91:844-851(1998) Fusion of TEL, the ETS-variant gene 6 (ETV6) , to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia.Peeters P., Raynaud S.D., Cools J., Wlodarska I., Grosgeorge J., Philip P., Monpoux F., Van Rompaey L., Baens M., Van Den Berghe H., Marynen P.Blood 90:2535-2540(1997) DNA sequence and analysis of human chromosome 9.Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.Nature 429:369-374(2004) The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity.Pollack B.P., Kotenko S.V., He W., Izotova L.S., Barnoski B.L., Pestka S.J. Biol. Chem. 274:31531-31542(1999) STAM2, a new member of the STAM family, binding to the Janus kinases.Endo K., Takeshita T., Kasai H., Sasaki Y., Tanaka N., Asao H., Kikuchi K., Yamada M., Chenb M., O'Shea J.J., Sugamura K.FEBS Lett. 477:55-61(2000) A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R.Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., Rennick D.M., Kastelein R.A., de Waal Malefyt R., Moore K.W.J. Immunol. 168:5699-5708(2002) The t(8;9) (p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2.Reiter A., Walz C., Watmore A., Schoch C., Blau I., Schlegelberger B., Berger U., Telford N., Aruliah S., Yin J.A., Vanstraelen D., Barker H.F., Taylor P.C., O'Driscoll A., Benedetti F., Rudolph C., Kolb H.-J., Hochhaus A., Hehlmann R., Chase A., Cross N.C.P.Cancer Res. 65:2662-2667(2005) PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation.Murati A., Gelsi-Boyer V., Adelaide J., Perot C., Talmant P., Giraudier S., Lode L., Letessier A., Delaval B., Brunel V., Imbert M., Garand R., Xerri L., Birnbaum D., Mozziconacci M.-J., Chaffanet M.Leukemia 19:1692-1696(2005) The t(8;9) (p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene.Bousquet M., Quelen C., De Mas V., Duchayne E., Roquefeuil B., Delsol G., Laurent G., Dastugue N., Brousset P.Oncogene 24:7248-7252(2005) A combination of cytomorphology, cytogenetic analysis, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for establishing clonality in cases of persisting hypereosinophilia.Bacher U., Reiter A., Haferlach T., Mueller L., Schnittger S., Kern W., Schoch C.Haematologica 91:817-820(2006) A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma.Adelaide J., Perot C., Gelsi-Boyer V., Pautas C., Murati A., Copie-Bergman C., Imbert M., Chaffanet M., Birnbaum D., Mozziconacci M.-J.Leukemia 20:536-537(2006) JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin.Dawson M.A., Bannister A.J., Gottgens B., Foster S.D., Bartke T., Green A.R., Kouzarides T.Nature 461:819-822(2009) Heme controls the regulation of protein tyrosine kinases Jak2 and Src.Yao X., Balamurugan P., Arvey A., Leslie C., Zhang L.Biochem. Biophys. Res. Commun. 403:30-35(2010) The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure.Guilluy C., Bregeon J., Toumaniantz G., Rolli-Derkinderen M., Retailleau K., Loufrani L., Henrion D., Scalbert E., Bril A., Torres R.M., Offermanns S., Pacaud P., Loirand G.Nat. Med. 16:183-190(2010) Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control.Jakel H., Weinl C., Hengst L.Oncogene 30:3502-3512(2011) Jak2 tyrosine kinase a mediator of both housekeeping and ligand-dependent gene expression?Wallace T.A., Sayeski P.P.Cell Biochem. Biophys. 44:213-222(2006) Janus kinases in immune cell signaling.Ghoreschi K., Laurence A., O'Shea J.J.Immunol. Rev. 228:273-287(2009) The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor.Lucet I.S., Fantino E., Styles M., Bamert R., Patel O., Broughton S.E., Walter M., Burns C.J., Treutlein H., Wilks A.F., Rossjohn J.Blood 107:176-183(2006) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.The cancer genome projectBaxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., Vassiliou G.S., Bench A.J., Boyd E.M., Curtin N., Scott M.A., Erber W.N., Green A.R.Lancet 365:1054-1061(2005) ErratumThe cancer genome projectBaxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., Vassiliou G.S., Bench A.J., Boyd E.M., Curtin N., Scott M.A., Erber W.N., Green A.R.Lancet 366:122-122(2005) Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status a prospective study.The United Kingdom myeloproliferative disorders study group, The medical research council adult leukaemia working party, The Australasian leukaemia and lymphoma groupCampbell P.J., Scott L.M., Buck G., Wheatley K., East C.L., Marsden J.T., Duffy A., Boyd E.M., Bench A.J., Scott M.A., Vassiliou G.S., Milligan D.W., Smith S.R., Erber W.N., Bareford D., Wilkins B.S., Reilly J.T., Harrison C.N., Green A.R.Lancet 366:1945-1953(2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.James C., Ugo V., Le Couedic J.-P., Staerk J., Delhommeau F., Lacout C., Garcon L., Raslova H., Berger R., Bennaceur-Griscelli A., Villeval J.L., Constantinescu S.N., Casadevall N., Vainchenker W.Nature 434:1144-1148(2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders.Kralovics R., Passamonti F., Buser A.S., Teo S.-S., Tiedt R., Passweg J.R., Tichelli A., Cazzola M., Skoda R.C.N. Engl. J. Med. 352:1779-1790(2005) Case records of the Massachusetts General Hospital. Case 15-2006 a 46-year-old woman with sudden onset of abdominal distention.Chung R.T., Iafrate A.J., Amrein P.C., Sahani D.V., Misdraji J.N. Engl. J. Med. 354:2166-2175(2006) The JAK2 V617F mutation in de novo acute myelogenous leukemias.Lee J.W., Kim Y.G., Soung Y.H., Han K.J., Kim S.Y., Rhim H.S., Min W.S., Nam S.W., Park W.S., Lee J.Y., Yoo N.J., Lee S.H.Oncogene 25:1434-1436(2006) The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation.Jamieson C.H.M., Gotlib J., Durocher J.A., Chao M.P., Mariappan M.R., Lay M., Jones C., Zehnder J.L., Lilleberg S.L., Weissman I.L.Proc. Natl. Acad. Sci. U.S.A. 103:6224-6229(2006) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis.Scott L.M., Tong W., Levine R.L., Scott M.A., Beer P.A., Stratton M.R., Futreal P.A., Erber W.N., McMullin M.F., Harrison C.N., Warren A.J., Gilliland D.G., Lodish H.F., Green A.R.N. Engl. J. Med. 356:459-468(2007) Patterns of somatic mutation in human cancer genomes.Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.Nature 446:153-158(2007) Germline JAK2 mutation in a family with hereditary thrombocytosis.Mead A.J., Rugless M.J., Jacobsen S.E., Schuh A.N. Engl. J. Med. 366:967-969(2012) +Additional computationally mapped references.<p>Provides general information on the entry.

Small volumes of JAK2 recombinant protein vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. If necessary, briefly centrifuge the vial on a tabletop centrifuge to dislodge any liquid in the container`s cap. Certain products may require to ship with dry ice and additional dry ice fee may apply.

MBS1066084 is a recombinant protein targeting JAK2. Also known as Recombinant Human Tyrosine-protein kinase JAK2. Host: E Coli or Yeast or Baculovirus or Mammalian Cell.