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Jak2 Information

Janus kinase 2 (commonly called JAK2) is a human 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.[1] JAK2 gene fusions with the TEL(ETV6) (TEL-JAK2) and PCM1 genes have been found in leukemia patients.[2][3] Further, mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, and other myeloproliferative disorders.[4] 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. Loss of Jak2 is lethal by embryonic day 12 in mice.[5]

JAK2 orthologs [6] have been identified in all mammals for which complete genome data are available.

Contents

Interactions

Janus kinase 2 has been shown to interact with Growth hormone receptor,[7][8][9] Protein arginine methyltransferase 5,[10] STAT5A,[11][12] STAT5B,[11][12] Interleukin 12 receptor, beta 2 subunit,[13] PIK3R1,[14] SH2B1,[15][16] SHC1,[17][18] TEC,[19][20] SOCS3,[21][22][23] PTPN11,[24][25][26] PTPN6,[27][28] Interleukin 5 receptor alpha subunit,[29] Grb2,[30][31] Suppressor of cytokine signaling 1,[32][33][34][35][36][23] VAV1,[37][38] FYN,[39] Epidermal growth factor receptor,[40] PTK2,[41][42] TNFRSF1A,[43] Erythropoietin receptor,[44][45] YES1,[14] IRS1,[46][47] DNAJA3,[48] Signal transducing adaptor molecule[49] and PPP2R4.[14]

References

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  2. ^ Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffé M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA (1997). "A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia". Science 278 (5341): 1309–12. doi:10.1126/science.278.5341.1309. PMID 9360930.
  3. ^ 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 (2005). "The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2". Cancer Res. 65 (7): 2662–7. doi:10.1158/0008-5472.CAN-04-4263. PMID 15805263.
  4. ^ Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC (2005). "A gain-of-function mutation of JAK2 in myeloproliferative disorders". N. Engl. J. Med. 352 (17): 1779–90. doi:10.1056/NEJMoa051113. PMID 15858187.
  5. ^ Neubauer H, Cumano A, Müller M, Wu H, Huffstadt U, Pfeffer K (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.
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  27. ^ Jiao, H; Berrada K, Yang W, Tabrizi M, Platanias L C, Yi T (Dec. 1996). "Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1". Mol. Cell. Biol. (UNITED STATES) 16 (12): 6985–92. ISSN 0270-7306. PMID 8943354.
  28. ^ Wu, D W; Stark K C, Dunnington D, Dillon S B, Yi T, Jones C, Pelus L M (Feb. 2000). "SH2-Containing protein tyrosine phosphatase-1 (SHP-1) association with Jak2 in UT-7/Epo cells". Blood Cells Mol. Dis. (UNITED STATES) 26 (1): 15–24. doi:10.1006/bcmd.2000.0273. ISSN 1079-9796. PMID 10772872.
  29. ^ Ogata, N; Kouro T, Yamada A, Koike M, Hanai N, Ishikawa T, Takatsu K (Apr. 1998). "JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation". Blood (UNITED STATES) 91 (7): 2264–71. ISSN 0006-4971. PMID 9516124.
  30. ^ Chauhan, D; Kharbanda S M, Ogata A, Urashima M, Frank D, Malik N, Kufe D W, Anderson K C (Dec. 1995). "Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells". J. Exp. Med. (UNITED STATES) 182 (6): 1801–6. doi:10.1084/jem.182.6.1801. ISSN 0022-1007. PMID 7500025.
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  32. ^ Yasukawa, H; Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle J N, Yoshimura A (Mar. 1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". EMBO J. (ENGLAND) 18 (5): 1309–20. doi:10.1093/emboj/18.5.1309. ISSN 0261-4189. PMID 10064597.
  33. ^ Dif, F; Saunier E, Demeneix B, Kelly P A, Edery M (Dec. 2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology (United States) 142 (12): 5286–93. doi:10.1210/en.142.12.5286. ISSN 0013-7227. PMID 11713228.
  34. ^ Endo, T A; Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (Jun. 1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature (ENGLAND) 387 (6636): 921–4. doi:10.1038/43213. ISSN 0028-0836. PMID 9202126.
  35. ^ Pezet, A; Favre H, Kelly P A, Edery M (Aug. 1999). "Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling". J. Biol. Chem. (UNITED STATES) 274 (35): 24497–502. doi:10.1074/jbc.274.35.24497. ISSN 0021-9258. PMID 10455112.
  36. ^ Ungureanu, Daniela; Saharinen Pipsa, Junttila Ilkka, Hilton Douglas J, Silvennoinen Olli (May. 2002). "Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1". Mol. Cell. Biol. (United States) 22 (10): 3316–26. doi:10.1128/MCB.22.10.3316-3326.2002. ISSN 0270-7306. PMID 11971965.
  37. ^ Shigematsu, H; Iwasaki H, Otsuka T, Ohno Y, Arima F, Niho Y (May. 1997). "Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity". J. Biol. Chem. (UNITED STATES) 272 (22): 14334–40. doi:10.1074/jbc.272.22.14334. ISSN 0021-9258. PMID 9162069.
  38. ^ Matsuguchi, T; Inhorn R C, Carlesso N, Xu G, Druker B, Griffin J D (Jan. 1995). "Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL". EMBO J. (ENGLAND) 14 (2): 257–65. ISSN 0261-4189. PMID 7530656.
  39. ^ Sayeski, P P; Ali M S, Safavi A, Lyles M, Kim S O, Frank S J, Bernstein K E (Nov. 1999). "A catalytically active Jak2 is required for the angiotensin II-dependent activation of Fyn". J. Biol. Chem. (UNITED STATES) 274 (46): 33131–42. doi:10.1074/jbc.274.46.33131. ISSN 0021-9258. PMID 10551884.
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  41. ^ Zhu, T; Goh E L, Lobie P E (Apr. 1998). "Growth hormone stimulates the tyrosine phosphorylation and association of p125 focal adhesion kinase (FAK) with JAK2. Fak is not required for stat-mediated transcription". J. Biol. Chem. (UNITED STATES) 273 (17): 10682–9. doi:10.1074/jbc.273.17.10682. ISSN 0021-9258. PMID 9553131.
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  46. ^ Gual, P; Baron V, Lequoy V, Van Obberghen E (Mar. 1998). "Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor". Endocrinology (UNITED STATES) 139 (3): 884–93. doi:10.1210/en.139.3.884. ISSN 0013-7227. PMID 9492017.
  47. ^ Kawazoe, Y; Naka T, Fujimoto M, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T (Jan. 2001). "Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1)/suppressor of cytokine signaling 1 (SOCS1) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 (IRS-1) phosphorylation". J. Exp. Med. (United States) 193 (2): 263–9. doi:10.1084/jem.193.2.263. ISSN 0022-1007. PMID 11208867.
  48. ^ Sarkar, S; Pollack B P, Lin K T, Kotenko S V, Cook J R, Lewis A, Pestka S (Dec. 2001). "hTid-1, a human DnaJ protein, modulates the interferon signaling pathway". J. Biol. Chem. (United States) 276 (52): 49034–42. doi:10.1074/jbc.M103683200. ISSN 0021-9258. PMID 11679576.
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Further reading

PDB Gallery
2b7a: The structural basis of Janus Kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor

External links

Protein kinases: tyrosine kinases (EC 2.7.10)
Receptor tyrosine kinases (EC 2.7.10.1)
EGF receptor family EGFR · ERBB2 · ERBB3 · ERBB4
Insulin receptor family IGF1R · INSR · INSRR
PDGF receptor family CSF1R · FLT3 · KIT · PDGFR (PDGFRA, PDGFRB)
FGF receptor family FGFR1 · FGFR2 · FGFR3 · FGFR4
VEGF receptors family VEGFR1 · VEGFR2 · VEGFR3 · VEGFR4
HGF receptor family MET · RON
Trk receptor family NTRK1 · NTRK2 · NTRK3
EPH receptor family EPHA1 · EPHA2 · EPHA3 · EPHA4 · EPHA5 · EPHA6 · EPHA7 · EPHA8 · EPHB1 · EPHB2 · EPHB3 · EPHB4 · EPHB5 · EPHB6 · EPHX
LTK receptor family LTK · ALK
TIE receptor family TIE · TEK
ROR receptor family ROR1 · ROR2
DDR receptor family DDR1 · DDR2
PTK7 receptor family PTK7
RYK receptor family RYK
MuSK receptor family MUSK
ROS receptor family ROS1
AATYK receptor family AATYK · AATYK2 · AATYK3
AXL receptor family AXL · MER · TYRO3
RET receptor family RET
uncatagorised STYK1
Non-receptor tyrosine kinases (EC 2.7.10.2)
ABL family ABL1 · ARG
ACK family ACK1 · TNK1
CSK family CSK · MATK
FAK family FAK · PYK2
FES family FES · FER
FRK family FRK · BRK · SRMS
JAK family JAK1 · JAK2 · JAK3 · TYK2
SRC-A family SRC · FGR · FYN · YES1
SRC-B family BLK · HCK · LCK · LYN
TEC family TEC · BMX · BTK · ITK · TXK
SYK family SYK · ZAP70

Categories: Human proteins

 

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