Janus Kinase 2 (JAK2)

JTK10; Tyrosine-protein kinase JAK2

SPN	R303
HGNC	6192
MGI	96629
PubMed	15858187
RGD	2939
UniProt	O60674

Janus kinase 2 is a protein that has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g. IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R). JAK2 signaling is activated downstream from the prolactin receptor. JAK2 gene fusions with the TEL(ETV6) (TEL-JAK2) and PCM1 genes have been found in leukemia patients. Further, mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, and other myeloproliferative disorders. This mutation, a change of valine to phenylalanine at the 617 position, appears to render hematopoietic cells more sensitive to growth factors such as erythropoietin and thrombopoietin.

Reference

"Cloning and characterization of human Jak-2 kinase: high mRNA expression in immune cells and muscle tissue."
Biochem. Biophys. Res. Commun. 246:627-633(1998) [PubMed] [Europe PMC] [Abstract]

"Cloning and characterization of the human homolog of mouse Jak2."
Blood 91:844-851(1998) [PubMed] [Europe PMC] [Abstract]

"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."
Blood 90:2535-2540(1997) [PubMed] [Europe PMC] [Abstract]

"DNA sequence and analysis of human chromosome 9."
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]

"The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity."
J. Biol. Chem. 274:31531-31542(1999) [PubMed] [Europe PMC] [Abstract]

"STAM2, a new member of the STAM family, binding to the Janus kinases."
FEBS Lett. 477:55-61(2000) [PubMed] [Europe PMC] [Abstract]

"A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R."
J. Immunol. 168:5699-5708(2002) [PubMed] [Europe PMC] [Abstract]

"The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2."
Cancer Res. 65:2662-2667(2005) [PubMed] [Europe PMC] [Abstract]

"PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation."
Leukemia 19:1692-1696(2005) [PubMed] [Europe PMC] [Abstract]

"The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene."
Oncogene 24:7248-7252(2005) [PubMed] [Europe PMC] [Abstract]

"A combination of cytomorphology, cytogenetic analysis, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for establishing clonality in cases of persisting hypereosinophilia."
Haematologica 91:817-820(2006) [PubMed] [Europe PMC] [Abstract]

"A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma."
Leukemia 20:536-537(2006) [PubMed] [Europe PMC] [Abstract]

"JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin."
Nature 461:819-822(2009) [PubMed] [Europe PMC] [Abstract]

"Heme controls the regulation of protein tyrosine kinases Jak2 and Src."
Biochem. Biophys. Res. Commun. 403:30-35(2010) [PubMed] [Europe PMC] [Abstract]

"The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure."
Nat. Med. 16:183-190(2010) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control."
Oncogene 30:3502-3512(2011) [PubMed] [Europe PMC] [Abstract]

"Jak2 tyrosine kinase: a mediator of both housekeeping and ligand-dependent gene expression?"
Cell Biochem. Biophys. 44:213-222(2006) [PubMed] [Europe PMC] [Abstract]

"Janus kinases in immune cell signaling."
Immunol. Rev. 228:273-287(2009) [PubMed] [Europe PMC] [Abstract]

"The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor."
Blood 107:176-183(2006) [PubMed] [Europe PMC] [Abstract]

"Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders."
Lancet 365:1054-1061(2005) [PubMed] [Europe PMC] [Abstract]

Erratum
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."
Lancet 366:1945-1953(2005) [PubMed] [Europe PMC] [Abstract]

"A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera."
Nature 434:1144-1148(2005) [PubMed] [Europe PMC] [Abstract]

"A gain-of-function mutation of JAK2 in myeloproliferative disorders."
N. Engl. J. Med. 352:1779-1790(2005) [PubMed] [Europe PMC] [Abstract]

"Case records of the Massachusetts General Hospital. Case 15-2006: a 46-year-old woman with sudden onset of abdominal distention."
N. Engl. J. Med. 354:2166-2175(2006) [PubMed] [Europe PMC] [Abstract]

"The JAK2 V617F mutation in de novo acute myelogenous leukemias."
Oncogene 25:1434-1436(2006) [PubMed] [Europe PMC] [Abstract]

"The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation."
Proc. Natl. Acad. Sci. U.S.A. 103:6224-6229(2006) [PubMed] [Europe PMC] [Abstract]

"JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis."
N. Engl. J. Med. 356:459-468(2007) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]

"Germline JAK2 mutation in a family with hereditary thrombocytosis."
N. Engl. J. Med. 366:967-969(2012) [PubMed] [Europe PMC] [Abstract]