Phospho-JAK2 (Y221) Polyclonal Antibody, 100 µg, (ATB-P0574)

Description

Background:

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.

Product datasheet:

References:

1. 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) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
2. 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) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
3. 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) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH ETV6.
4. 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) [PubMed] [Europe PMC]

   Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

5. 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) [PubMed] [Europe PMC] Cited for: INTERACTION WITH SKB1.
6. 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) [PubMed] [Europe PMC] Cited for: INTERACTION WITH STAM2. Tissue: Fetal brain.
7. 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) [PubMed] [Europe PMC]

   Cited for: FUNCTION, INTERACTION WITH IL23R.

8. 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) [PubMed] [Europe PMC]

   Cited for: CHROMOSOMAL TRANSLOCATION WITH PCM1.

9. 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) [PubMed] [Europe PMC] Cited for: CHROMOSOMAL TRANSLOCATION WITH PCM1.
10. 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) [PubMed] [Europe PMC] Cited for: CHROMOSOMAL TRANSLOCATION WITH PCM1.