Wikipedia

Janus kinase 2

Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and 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).[5][6]

JAK2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesJAK2, JTK10, THCYT3, Janus kinase 2, MAX2
External IDsOMIM: 147796; MGI: 96629; HomoloGene: 21033; GeneCards: JAK2; OMA:JAK2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

3717

16452

Ensembl

ENSG00000096968

ENSMUSG00000024789

UniProt

O60674

Q62120

RefSeq (mRNA)

NM_001048177
NM_008413

RefSeq (protein)

NP_001041642
NP_032439

Location (UCSC)Chr 9: 4.98 – 5.13 MbChr 19: 29.23 – 29.29 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains (SH2/SH3) and the presence of up to seven JAK homology domains (JH1-JH7). Nonetheless the terminal JH domains retain a high level of homology to tyrosine kinase domains. An interesting note is that only one of these carboxy-terminal JH domains retains full kinase function (JH1) while the other (JH2), previously thought to have no kinase functionality and accordingly termed a pseudokinase domain, has since been found to be catalytically active, albeit at only 10% that of the JH1 domain.[7][8]

Loss of JAK2 is lethal by embryonic day 12 in mice.[9]

JAK2 orthologs[10] have been identified in all mammals for which complete genome data are available.

Clinical significance

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JAK2 gene fusions with the TEL(ETV6) (TEL-JAK2) and PCM1 genes have been found in patients suffering leukemia, particularly clonal eosinophilia forms of the disease.[11][12][13]

Mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, and myelofibrosis as well as other myeloproliferative disorders.[14] This mutation (V617F), 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, because the receptors for these growth factors require JAK2 for signal transduction. JAK2 mutation, when demonstrable, is one of the methods of diagnosing polycythemia vera.[15]

Interactions

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Janus kinase 2 has been shown to interact with:

Prolactin signals through JAK2 are dependent on STAT5, and on the RUSH transcription factors.[59]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000096968 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024789 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (June 1998). "Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice". Endocrine Reviews. 19 (3): 225–68. doi:10.1210/edrv.19.3.0334. PMID 9626554.
  6. ^ Brooks AJ, Dai W, O'Mara ML, Abankwa D, Chhabra Y, Pelekanos RA, et al. (2014). "Mechanism of activation of protein kinase JAK2 by the growth hormone receptor". Science. 344 (6185): 1249783. doi:10.1126/science.1249783. PMID 24833397. S2CID 27946074.
  7. ^ Morgan KJ, Gilliland DG (2008). "A role for JAK2 mutations in myeloproliferative diseases". Annual Review of Medicine. 59 (1): 213–22. doi:10.1146/annurev.med.59.061506.154159. PMID 17919086.
  8. ^ Ungureanu D, Wu J, Pekkala T, Niranjan Y, Young C, Jensen ON, Xu CF, Neubert TA, Skoda RC, Hubbard SR, Silvennoinen O (August 2011). "The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling". Nature Structural & Molecular Biology. 18 (9): 971–976. doi:10.1038/nsmb.2099. PMC 4504201. PMID 21841788.
  9. ^ Neubauer H, Cumano A, Müller M, Wu H, Huffstadt U, Pfeffer K (May 1998). "Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis". Cell. 93 (3): 397–409. doi:10.1016/S0092-8674(00)81168-X. PMID 9590174. S2CID 11375232.
  10. ^ "OrthoMaM phylogenetic marker: JAK2 coding sequence".[permanent dead link‍]
  11. ^ Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffé M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA (November 1997). "A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia". Science. 278 (5341): 1309–12. Bibcode:1997Sci...278.1309L. doi:10.1126/science.278.5341.1309. PMID 9360930.
  12. ^ Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, Yin JA, Vanstraelen D, Barker HF, Taylor PC, O'Driscoll A, Benedetti F, Rudolph C, Kolb HJ, Hochhaus A, Hehlmann R, Chase A, Cross NC (April 2005). "The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2". Cancer Research. 65 (7): 2662–7. doi:10.1158/0008-5472.CAN-04-4263. PMID 15805263.
  13. ^ Reiter A, Gotlib J (2017). "Myeloid neoplasms with eosinophilia". Blood. 129 (6): 704–714. doi:10.1182/blood-2016-10-695973. PMID 28028030.
  14. ^ Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC (April 2005). "A gain-of-function mutation of JAK2 in myeloproliferative disorders". The New England Journal of Medicine. 352 (17): 1779–90. doi:10.1056/NEJMoa051113. hdl:11383/2023329. PMID 15858187.
  15. ^ Scott LM (August 2011). "The JAK2 exon 12 mutations: a comprehensive review". American Journal of Hematology. 86 (8): 668–76. doi:10.1002/ajh.22063. PMID 21674578. S2CID 2905512.
  16. ^ Sarkar S, Pollack BP, Lin KT, Kotenko SV, Cook JR, Lewis A, Pestka S (December 2001). "hTid-1, a human DnaJ protein, modulates the interferon signaling pathway". The Journal of Biological Chemistry. 276 (52): 49034–42. doi:10.1074/jbc.M103683200. PMID 11679576.
  17. ^ Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE (June 1999). "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". The Journal of Biological Chemistry. 274 (24): 17209–18. doi:10.1074/jbc.274.24.17209. PMID 10358079.
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  32. ^ Ryu H, Lee JH, Kim KS, Jeong SM, Kim PH, Chung HT (August 2000). "Regulation of neutrophil adhesion by pituitary growth hormone accompanies tyrosine phosphorylation of Jak2, p125FAK, and paxillin". Journal of Immunology. 165 (4): 2116–23. doi:10.4049/jimmunol.165.4.2116. PMID 10925297.
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  36. ^ Jiao H, Berrada K, Yang W, Tabrizi M, Platanias LC, Yi T (December 1996). "Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1". Molecular and Cellular Biology. 16 (12): 6985–92. doi:10.1128/mcb.16.12.6985. PMC 231702. PMID 8943354.
  37. ^ Wu DW, Stark KC, Dunnington D, Dillon SB, Yi T, Jones C, Pelus LM (February 2000). "SH2-Containing protein tyrosine phosphatase-1 (SHP-1) association with Jak2 in UT-7/Epo cells". Blood Cells, Molecules & Diseases. 26 (1): 15–24. doi:10.1006/bcmd.2000.0273. PMID 10772872.
  38. ^ Pollack BP, Kotenko SV, He W, Izotova LS, Barnoski BL, Pestka S (October 1999). "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity". The Journal of Biological Chemistry. 274 (44): 31531–42. doi:10.1074/jbc.274.44.31531. PMID 10531356.
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  45. ^ a b Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications. 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID 9344848.
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  53. ^ Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O (May 2002). "Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1". Molecular and Cellular Biology. 22 (10): 3316–26. doi:10.1128/MCB.22.10.3316-3326.2002. PMC 133778. PMID 11971965.
  54. ^ Takahashi-Tezuka M, Hibi M, Fujitani Y, Fukada T, Yamaguchi T, Hirano T (May 1997). "Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK". Oncogene. 14 (19): 2273–82. doi:10.1038/sj.onc.1201071. PMID 9178903.
  55. ^ Yamashita Y, Watanabe S, Miyazato A, Ohya Ki, Ikeda U, Shimada K, Komatsu N, Hatake K, Miura Y, Ozawa K, Mano H (March 1998). "Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription". Blood. 91 (5): 1496–507. doi:10.1182/blood.V91.5.1496. PMID 9473212.
  56. ^ Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB (March 1998). "Induction of Jak/STAT signaling by activation of the type 1 TNF receptor". Journal of Immunology. 160 (6): 2742–50. doi:10.4049/jimmunol.160.6.2742. PMID 9510175.
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  59. ^ Helmer RA, Panchoo M, Dertien JS, Bhakta SM, Hewetson A, Chilton BS (August 2010). "Prolactin-induced Jak2 phosphorylation of RUSH: a key element in Jak/RUSH signaling". Molecular and Cellular Endocrinology. 325 (1–2): 143–9. doi:10.1016/j.mce.2010.05.010. PMC 2902710. PMID 20562009.

Further reading

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