JAK2

Official Full Name

Janus kinase 2

Organism

Homo sapiens

Gene ID

3717

Background

This gene encodes a non-receptor tyrosine kinase that plays a central role in cytokine and growth factor signalling. The primary isoform of this protein has an N-terminal FERM domain that is required for erythropoietin receptor association, an SH2 domain that binds STAT transcription factors, a pseudokinase domain and a C-terminal tyrosine kinase domain. Cytokine binding induces autophosphorylation and activation of this kinase. This kinase then recruits and phosphorylates signal transducer and activator of transcription (STAT) proteins. Growth factors like TGF-beta 1 also induce phosphorylation and activation of this kinase and translocation of downstream STAT proteins to the nucleus where they influence gene transcription. Mutations in this gene are associated with numerous inflammatory diseases and malignancies. This gene is a downstream target of the pleiotropic cytokine IL6 that is produced by B cells, T cells, dendritic cells and macrophages to produce an immune response or inflammation. Disregulation of the IL6/JAK2/STAT3 signalling pathways produces increased cellular proliferation and myeloproliferative neoplasms of hematopoietic stem cells. A nonsynonymous mutation in the pseudokinase domain of this gene disrupts the domains inhibitory effect and results in constitutive tyrosine phosphorylation activity and hypersensitivity to cytokine signalling. This gene and the IL6/JAK2/STAT3 signalling pathway is a therapeutic target for the treatment of excessive inflammatory responses to viral infections. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2020]

Synonyms

JTK10

Bio Chemical Class

Kinase

Protein Sequence

MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSETERIWYPPNHVFHIDESTRHNVLYRIRFYFPRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLGMAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQFSQCKATARNLKLKYLINLETLQSAFYTEKFEVKEPGSGPSGEEIFATIIITGNGGIQWSRGKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLREALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQTGLYVLRCSPKDFNKYFLTFAVERENVIEYKHCLITKNENEEYNLSGTKKNFSSLKDLLNCYQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKIRNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASMMSKLSHKHLVLNYGVCVCGDENILVQEFVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVPPECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAELANLINNCMDYEPDFRPSFRAIIRDLNSLFTPDYELLTENDMLPNMRIGALGFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKQGQMIVFHLIELLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQIRDNMAG

Open

Disease

Acquired hypomelanotic disorder, Alopecia, Asthma, Atopic eczema, B-cell lymphoma, Breast cancer, Diffuse large B-cell lymphoma, Leukaemia, Liver cancer, Lung cancer, Lupus erythematosus, Malignant haematopoietic neoplasm, Multiple myeloma, Multiple sclerosis, Muscular dystrophy, Myeloproliferative neoplasm, Pancreatic cancer, Rheumatoid arthritis, Solid tumour/cancer, Thrombocytosis, Transplant rejection

Approved Drug

5 +

Clinical Trial Drug

20 +

Discontinued Drug

1 +

Cat.No.	Product Name	Price
CSC-DC007850	Panoply™ Human JAK2 Knockdown Stable Cell Line	Inquiry
CSC-SC007850	Panoply™ Human JAK2 Over-expressing Stable Cell Line	Inquiry
CSC-RT1909	JAK2 Knockout Cell Line-HeLa	Inquiry
CSC-RT2191	Human JAK2 Knockout Cell Line-A549	Inquiry
CLKO-1764	JAK2 KO Cell Lysate-HeLa	Inquiry
CSC-RO0419	Human JAK2_V617F Stable Cell Line - Ba/F3	Inquiry

Cat.No.	Product Name	Price
AD00099Z	Human JAK1 adenoviral particles	Inquiry
AD08311Z	Human JAK2 adenoviral particles	Inquiry
LV15820L	human JAK2 (NM_004972) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH321927	shRNA set against Mouse JAK2 (NM_008413.2)	Inquiry
SHH321931	shRNA set against Rat JAK2 (NM_031514.1)	Inquiry
SHL185538	shRNA set against Mouse Jak2(NM_001048177.1)	Inquiry
SHL185622	shRNA set against Mouse Jak2(NM_008413.2)	Inquiry
SHH321923	shRNA set against Human JAK2 (NM_004972.3)	Inquiry
SHL185561	shRNA set against Rat Jak2(NM_031514.1)	Inquiry
SHW001194	shRNA set against Chicken JAK2 (NM_001030538)	Inquiry
SHW014599	shRNA set against Danio rerio JAK2B (NM_131087)	Inquiry

Cat.No.	Product Name	Price
CDCL185007	Human JAK2 ORF clone(NM_004972.3)	Inquiry
CDFR012676	Rat Jak2 cDNA Clone(NM_031514.1)	Inquiry
MiUTR1M-06179	JAK2 miRNA 3'UTR clone	Inquiry
MiUTR1M-06180	JAK2 miRNA 3'UTR clone	Inquiry
MiUTR1R-02730	JAK2 miRNA 3'UTR clone	Inquiry
MiUTR3H-01246	JAK2 miRNA 3'UTR clone	Inquiry
CDCB162669	Chicken JAK2 ORF Clone (NM_001030538)	Inquiry
CDCB176074	Danio rerio JAK2B ORF Clone (NM_131087)	Inquiry
CDCB180467	Rabbit JAK2 ORF clone (XM_002708002.2)	Inquiry
CDCL122309	Human Jak2 ORF clone (NM_008413.2)	Inquiry
CDCR233839	Mouse Jak2 ORF Clone(NM_001048177.1)	Inquiry
CDCR379709	Rat Jak2 ORF Clone(NM_031514.1)	Inquiry

Cat.No.	Product Name	Price
CC-723	JAK2 Easy KO Kit	Inquiry

Detailed Information

Recent Research

The Jak family of protein tyrosine kinases consists of four members (Jak1, Jak2, Jak3, and Tyk2) that are differentially activated in the response to various cytokines. Janus kinase 2 (JAK2) has been shown to be the predominant Jak activated in the response to a wide variety of cytokines, including Epo, IL-3, and granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-5, thrombopoietin (Tpo) growth hormone and prolactin. Besides, JAK2 is closely related to a variety of diseases.

Philadelphia chromosome (Ph)–negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis(PMF).Some clinical signs of the disease, such ascytopenias, splenomegaly, poor quality of life, shortened survival and the risk of transformation to acute myeloid leukemia (AML). Most patients carry a gain-of-function mutation in the JAK2. Studies have shown that in about 95% of subjects with PV and in about 60% of those with ET or PMF. Somatic mutations of JAK2 exon are found in the remaining 5% of patients with PV, whereas mutations of MPL exon are present in about 5% of those with ET or PMF. Some reports show that JAK2-mutated ET and PV form a biological continuum in which the degree of erythrocytosis is determined byphysiological and genetic modifiers. Patients with myelofibrosis secondary to ET or PV had significantly higher values for JAK2-mutant alleleburden than those with the primary MPN.

Alterations in JAK2 signaling cause profound changes in the cellular response to cytokine stimulation. TGF-β1 signaling induces phosphorylation and activation of JAK2, JAK2 and its phosphorylated form are typically located in the cytoplasm. Then JAK2 interacts and phosphorylates signal transducer and activator of transcription3 (STAT3) to induce fibrotic responses. In addition, JAK2 can be activated by other profibrotic mediators, including PDGF, VEGF, interleukin (IL)-6, IL-13, angiotensin II (ANGII), serotonin (5-HT) and endothelin (ET-1).

Some reports have shown that, in homogenized lung tissue, JAK2 and STAT3 mRNA transcript levels were both higher in IPF patients, as were JAK2 and STAT3 protein expression. The active phosphorylated forms of JAK2 and STAT3 were up-regulated in IPF lung tissue, JAK2 and STAT3 activation contributed to cell transformations typical of IPF, including the ATII to mesenchymal and fibroblast to myofibroblast transitions and fibroblast proliferation and migration. The nuclei level of cells in fibrotic areas of the lung implies that these proteins function as transcription factors. In addition, JAK2 and STAT3 exhibited independent effects on autophagy and senescence, with dual JAK2 and STAT3 inhibition leading to greater reductions in cell senescence and higher levels of autophagy than achieved by inhibiting either protein alone.

References:

Rumi E, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood, 2014, 123(10):1544-1551.
Verstovsek S, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. New England Journal of Medicine, 2015, 363(12):1117.
Milara J,et al. The JAK2 pathway is activated in idiopathic pulmonary fibrosis. Respiratory Research, 2018, 19(1):24.
Anelli L, et al. The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?International Journal of Molecular Sciences,2018,19(4).

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