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an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/02/04 22:10:07」(JST)

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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). JAK2 signaling is activated downstream from the prolactin receptor.^[1]

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 its function whilst the other, due to lacking important amino acids for kinase functionality, does not work; it is therefore termed as the pseudokinase domain.^[2]

Loss of Jak2 is lethal by embryonic day 12 in mice.^[3]

JAK2 orthologs ^[4] have been identified in all mammals for which complete genome data are available.

Clinical significance

JAK2 gene fusions with the TEL(ETV6) (TEL-JAK2) and PCM1 genes have been found in leukemia patients.^[5]^[6] Jak - 2 kinase mutations were found to have a high correlation with abnormal heart defects in those of Southeast Asian descent carrying the PYFA gene.^[5]^[6] Mutations in JAK2 have been implicated in polycythemia vera, essential thrombocythemia, and myelofibrosis as well as other myeloproliferative disorders.^[7] 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. An inhibitor of JAK2-STAT5, AZD1480, was pointed as having activity in primary and CRPC.^[8] Jak2 mutation when demonstratable is one of the methods of diagnosing Polycythemia Rubra Vera.^[9]

Interactions

Janus kinase 2 has been shown to interact with:

DNAJA3,^[10]
EGFR,^[11]
EPOR,^[12]^[13]
FYN,^[14]
Grb2,^[15]^[16]
GHR,^[17]^[18]^[19]
IRS1,^[20]^[21]
IL12RB2,^[22]
IL5RA,^[23]
PIK3R1,^[24]
PPP2R4,^[24]
PTK2,^[25]^[26]
PTPN11,^[27]^[28]^[29]
PTPN6,^[30]^[31]
PRMT5,^[32]
SH2B1,^[33]^[34]
SHC1,^[35]^[36]
SOCS3,^[37]^[38]^[39]
STAT5A,^[40]^[41]
STAT5B,^[40]^[41]
STAM,^[42]
SOCS1,^[39]^[43]^[44]^[45]^[46]^[47]
TEC,^[48]^[49]
TNFRSF1A,^[50]
VAV1,^[51]^[52] and
YES1.^[24]

Prolactin signals through JAK2 are dependent on STAT5, and on the RUSH transcription factors.^[53]

References

^ Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (1998). "Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice". Endocr. Rev. 19 (3): 225–68. doi:10.1210/er.19.3.225. PMID 9626554.
^ Morgan KJ, Gilliland DG (2008). "A role for JAK2 mutations in myeloproliferative diseases". Annu. Rev. Med. 59: 213–22. doi:10.1146/annurev.med.59.061506.154159. PMID 17919086.
^ 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.
^ "OrthoMaM phylogenetic marker: JAK2 coding sequence".
^ ^a ^b 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.
^ ^a ^b 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.
^ 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.
^ Gu L, Liao Z, Hoang DT, Dagvadorj A, Gupta S, Blackmon S, Ellsworth E, Talati P, Leiby B, Zinda M, Lallas CD, Trabulsi EJ, McCue P, Gomella L, Huszar D, Nevalainen MT (October 2013). "Pharmacologic Inhibition of Jak2-Stat5 Signaling By Jak2 Inhibitor AZD1480 Potently Suppresses Growth of Both Primary and Castrate-Resistant Prostate Cancer". Clin. Cancer Res. 19 (20): 5658–74. doi:10.1158/1078-0432.CCR-13-0422. PMID 23942095.
^ Scott LM (2011). "The JAK2 exon 12 mutations: a comprehensive review". Am. J. Hematol. 86 (8): 668–76. doi:10.1002/ajh.22063. PMID 21674578.
^ Sarkar S, Pollack BP, Lin KT, Kotenko SV, Cook JR, Lewis A, Pestka S (2001). "hTid-1, a human DnaJ protein, modulates the interferon signaling pathway". J. Biol. Chem. 276 (52): 49034–42. doi:10.1074/jbc.M103683200. PMID 11679576.
^ Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE (1999). "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". J. Biol. Chem. 274 (24): 17209–18. doi:10.1074/jbc.274.24.17209. PMID 10358079.
^ Huang LJ, Constantinescu SN, Lodish HF (2001). "The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor". Mol. Cell 8 (6): 1327–38. doi:10.1016/S1097-2765(01)00401-4. PMID 11779507.
^ Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN (1993). "JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin". Cell 74 (2): 227–36. doi:10.1016/0092-8674(93)90414-L. PMID 8343951.
^ Sayeski PP, Ali MS, Safavi A, Lyles M, Kim SO, Frank SJ, Bernstein KE (1999). "A catalytically active Jak2 is required for the angiotensin II-dependent activation of Fyn". J. Biol. Chem. 274 (46): 33131–42. doi:10.1074/jbc.274.46.33131. PMID 10551884.
^ Chauhan D, Kharbanda SM, Ogata A, Urashima M, Frank D, Malik N, Kufe DW, Anderson KC (1995). "Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells". J. Exp. Med. 182 (6): 1801–6. doi:10.1084/jem.182.6.1801. PMC 2192257. PMID 7500025.
^ Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (1995). "Involvement of Janus kinases in the insulin signaling pathway". Eur. J. Biochem. 234 (2): 656–60. doi:10.1111/j.1432-1033.1995.656_b.x. PMID 8536716.
^ Frank SJ, Yi W, Zhao Y, Goldsmith JF, Gilliland G, Jiang J, Sakai I, Kraft AS (1995). "Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor". J. Biol. Chem. 270 (24): 14776–85. doi:10.1074/jbc.270.24.14776. PMID 7540178.
^ VanderKuur JA, Wang X, Zhang L, Campbell GS, Allevato G, Billestrup N, Norstedt G, Carter-Su C (1994). "Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase". J. Biol. Chem. 269 (34): 21709–17. PMID 8063815.
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^ Kawazoe Y, Naka T, Fujimoto M, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T (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. 193 (2): 263–9. doi:10.1084/jem.193.2.263. PMC 2193341. PMID 11208867.
^ Yamamoto K, Shibata F, Miura O, Kamiyama R, Hirosawa S, Miyasaka N (1999). "Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus". Biochem. Biophys. Res. Commun. 257 (2): 400–4. doi:10.1006/bbrc.1999.0479. PMID 10198225.
^ Ogata N, Kouro T, Yamada A, Koike M, Hanai N, Ishikawa T, Takatsu K (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 91 (7): 2264–71. PMID 9516124.
^ ^a ^b ^c Fuhrer DK, Yang YC (1996). "Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11". Biochem. Biophys. Res. Commun. 224 (2): 289–96. doi:10.1006/bbrc.1996.1023. PMID 8702385.
^ Zhu T, Goh EL, Lobie PE (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. 273 (17): 10682–9. doi:10.1074/jbc.273.17.10682. PMID 9553131.
^ Ryu H, Lee JH, Kim KS, Jeong SM, Kim PH, Chung HT (2000). "Regulation of neutrophil adhesion by pituitary growth hormone accompanies tyrosine phosphorylation of Jak2, p125FAK, and paxillin". J. Immunol. 165 (4): 2116–23. doi:10.4049/jimmunol.165.4.2116. PMID 10925297.
^ Yin T, Shen R, Feng GS, Yang YC (1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases". J. Biol. Chem. 272 (2): 1032–7. doi:10.1074/jbc.272.2.1032. PMID 8995399.
^ Tauchi T, Damen JE, Toyama K, Feng GS, Broxmeyer HE, Krystal G (1996). "Tyrosine 425 within the activated erythropoietin receptor binds Syp, reduces the erythropoietin required for Syp tyrosine phosphorylation, and promotes mitogenesis". Blood 87 (11): 4495–501. PMID 8639815.
^ Maegawa H, Kashiwagi A, Fujita T, Ugi S, Hasegawa M, Obata T, Nishio Y, Kojima H, Hidaka H, Kikkawa R (1996). "SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates". Biochem. Biophys. Res. Commun. 228 (1): 122–7. doi:10.1006/bbrc.1996.1626. PMID 8912646.
^ Jiao H, Berrada K, Yang W, Tabrizi M, Platanias LC, Yi T (1996). "Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1". Mol. Cell. Biol. 16 (12): 6985–92. PMC 231702. PMID 8943354.
^ Wu DW, Stark KC, Dunnington D, Dillon SB, Yi T, Jones C, Pelus LM (2000). "SH2-Containing protein tyrosine phosphatase-1 (SHP-1) association with Jak2 in UT-7/Epo cells". Blood Cells Mol. Dis. 26 (1): 15–24. doi:10.1006/bcmd.2000.0273. PMID 10772872.
^ Pollack BP, Kotenko SV, He W, Izotova LS, Barnoski BL, Pestka S (1999). "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity". J. Biol. Chem. 274 (44): 31531–42. doi:10.1074/jbc.274.44.31531. PMID 10531356.
^ Rui L, Mathews LS, Hotta K, Gustafson TA, Carter-Su C (1997). "Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling". Mol. Cell. Biol. 17 (11): 6633–44. PMC 232517. PMID 9343427.
^ Xie S, Lin H, Sun T, Arlinghaus RB (2002). "Jak2 is involved in c-Myc induction by Bcr-Abl". Oncogene 21 (47): 7137–46. doi:10.1038/sj.onc.1205942. PMID 12370803.
^ VanderKuur J, Allevato G, Billestrup N, Norstedt G, Carter-Su C (1995). "Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2". J. Biol. Chem. 270 (13): 7587–93. doi:10.1074/jbc.270.13.7587. PMID 7535773.
^ Giordano V, De Falco G, Chiari R, Quinto I, Pelicci PG, Bartholomew L, Delmastro P, Gadina M, Scala G (1997). "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. 158 (9): 4097–103. PMID 9126968.
^ Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A (2000). "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2". J. Biol. Chem. 275 (38): 29338–47. doi:10.1074/jbc.M003456200. PMID 10882725.
^ Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A (1999). "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes Cells 4 (6): 339–51. doi:10.1046/j.1365-2443.1999.00263.x. PMID 10421843.
^ ^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 (1997). "Cloning and characterization of novel CIS family genes". Biochem. Biophys. Res. Commun. 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID 9344848.
^ ^a ^b Barahmand-Pour F, Meinke A, Groner B, Decker T (1998). "Jak2-Stat5 interactions analyzed in yeast". J. Biol. Chem. 273 (20): 12567–75. doi:10.1074/jbc.273.20.12567. PMID 9575217.
^ ^a ^b Fujitani Y, Hibi M, Fukada T, Takahashi-Tezuka M, Yoshida H, Yamaguchi T, Sugiyama K, Yamanaka Y, Nakajima K, Hirano T (1997). "An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT". Oncogene 14 (7): 751–61. doi:10.1038/sj.onc.1200907. PMID 9047382.
^ Takeshita T, Arita T, Higuchi M, Asao H, Endo K, Kuroda H, Tanaka N, Murata K, Ishii N, Sugamura K (1997). "STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction". Immunity 6 (4): 449–57. doi:10.1016/S1074-7613(00)80288-5. PMID 9133424.
^ Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". EMBO J. 18 (5): 1309–20. doi:10.1093/emboj/18.5.1309. PMC 1171221. PMID 10064597.
^ Dif F, Saunier E, Demeneix B, Kelly PA, Edery M (2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology 142 (12): 5286–93. doi:10.1210/en.142.12.5286. PMID 11713228.
^ Endo TA, 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 (1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature 387 (6636): 921–4. doi:10.1038/43213. PMID 9202126.
^ Pezet A, Favre H, Kelly PA, Edery M (1999). "Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling". J. Biol. Chem. 274 (35): 24497–502. doi:10.1074/jbc.274.35.24497. PMID 10455112.
^ Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O (2002). "Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1". Mol. Cell. Biol. 22 (10): 3316–26. doi:10.1128/MCB.22.10.3316-3326.2002. PMC 133778. PMID 11971965.
^ Takahashi-Tezuka M, Hibi M, Fujitani Y, Fukada T, Yamaguchi T, Hirano T (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.
^ Yamashita Y, Watanabe S, Miyazato A, Ohya Ki, Ikeda U, Shimada K, Komatsu N, Hatake K, Miura Y, Ozawa K, Mano H (1998). "Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription". Blood 91 (5): 1496–507. PMID 9473212.
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^ Shigematsu H, Iwasaki H, Otsuka T, Ohno Y, Arima F, Niho Y (1997). "Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity". J. Biol. Chem. 272 (22): 14334–40. doi:10.1074/jbc.272.22.14334. PMID 9162069.
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^ 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". Mol. Cell. Endocrinol. 325 (1-2): 143–9. doi:10.1016/j.mce.2010.05.010. PMC 2902710. PMID 20562009.

External links

Janus Kinase 2 at the US National Library of Medicine Medical Subject Headings (MeSH)

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1. 骨髄増殖性腫瘍の概要 overview of the myeloproliferative neoplasms
2. 真性多血症が疑われる患者に対する診断的アプローチ diagnostic approach to the patient with suspected polycythemia vera
3. 血小板増加症患者に対するアプローチ approach to the patient with thrombocytosis
4. 先天性赤血球増多症および真性多血症の分子学的病因 molecular pathogenesis of congenital polycythemic disorders and polycythemia vera
5. 本態性血小板血症の診断および臨床症状 diagnosis and clinical manifestations of essential thrombocythemia

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In vitro characterization and endocrine regulation of cholesterol and phospholipid transport in the mammary gland.

Ontsouka CE1, Huang X1, Aliyev E2, Albrecht C3.
Molecular and cellular endocrinology.Mol Cell Endocrinol.2017 Jan 5;439:35-45. doi: 10.1016/j.mce.2016.10.016. Epub 2016 Oct 17.
Cell-based studies previously showed that the ATP-binding cassette transporter A1 (ABCA1) transfers cholesterol across mammary epithelial cells (MEC). Data for phospholipid transport are lacking, and it is unclear from which cellular source the transported cholesterol stems, whether this transport a
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Natural killer cell-mediated cytotoxicity is increased by a type II arabinogalactan from Anoectochilus formosanus.

Yang LC1, Lai CY2, Lin WC3.
Carbohydrate polymers.Carbohydr Polym.2017 Jan 2;155:466-474. doi: 10.1016/j.carbpol.2016.08.086. Epub 2016 Aug 28.
This study investigated the effects of a type II arabinogalactan from Anoectochilus formosanus (AGAF) on natural killer (NK) cell-mediated cytotoxicity and the possible underlying mechanisms. This study reported that sustained exposure to AGAF increased NK-92MI cell-mediated cytotoxicity in a time-
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Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis.

Klein S1, Rick J1, Lehmann J1, Schierwagen R1, Schierwagen IG2, Verbeke L3, Hittatiya K4, Uschner FE1, Manekeller S5, Strassburg CP1, Wagner KU6, Sayeski PP7, Wolf D8, Laleman W3, Sauerbruch T1, Trebicka J1.
Gut.Gut.2017 Jan;66(1):145-155. doi: 10.1136/gutjnl-2015-309600. Epub 2015 Sep 17.
OBJECTIVE: Angiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and subsequently RHOA/Rho-kinase (ROCK), which induces experimental and probably human liver fibrosis. This study investigated the relationship of JAK2 to experimental and huma
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Japanese Journal

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes via Inhibition of JAK2 : Its Implication for Vitiligo Treatment

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NAID 40020633475

3) ゴナドトロピン受容体の機能にその構造及び生理活性物質が及ぼす影響(シンポジウム1(生殖) 卵巣のダイナミックな変化の神秘に迫る-臨床へのフィードバックを目指して-,第67回日本産科婦人科学会学術講演会講演要旨)

日本産科婦人科學會雜誌 67(10), 2167-2176, 2015-10-01
NAID 110009989073

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes via Inhibition of JAK2: Its Implication for Vitiligo Treatment

Biological and Pharmaceutical Bulletin 38(11), 1700-1706, 2015
NAID 130005106369

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関連記事	「kinase」「janus」

「kinase」

Janus kinase 2
	; PDB rendering based on 2b7a.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2B7A, 2W1I, 2XA4, 3E62, 3E63, 3E64, 3FUP, 3IO7, 3IOK, 3JY9, 3KCK, 3KRR, 3LPB, 3Q32, 3RVG, 3TJC, 3TJD, 3UGC, 3ZMM, 4AQC, 4BBE, 4BBF, 4C61, 4C62, 4E4M, 4E6D, 4E6Q, 4F08, 4F09, 4FVP, 4FVQ, 4FVR, 4GFM, 4GMY, 4HGE, 4IVA, 4JI9, 4JIA
Identifiers
Symbols	JAK2 ; JTK10; THCYT3
External IDs	OMIM: 147796 HomoloGene: 21033 ChEMBL: 2971 GeneCards: JAK2 Gene
EC number	2.7.10.2
Gene ontology
Molecular function	• protein kinase activity; • protein tyrosine kinase activity; • non-membrane spanning protein tyrosine kinase activity; • receptor binding; • growth hormone receptor binding; • interleukin-12 receptor binding; • protein binding; • ATP binding; • protein C-terminus binding; • protein kinase binding; • heme binding; • type 1 angiotensin receptor binding; • acetylcholine receptor binding; • histone kinase activity (H3-Y41 specific); • SH2 domain binding; • histone binding; • phosphatidylinositol 3-kinase binding; • insulin receptor substrate binding; • peptide hormone receptor binding;
Cellular component	• nucleus; • cytoplasm; • cytosol; • cytoskeleton; • caveola; • nuclear matrix; • endosome lumen; • membrane raft;
Biological process	• activation of MAPKK activity; • protein phosphorylation; • apoptotic process; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • cellular component movement; • signal transduction; • enzyme linked receptor protein signaling pathway; • G-protein coupled receptor signaling pathway; • positive regulation of cytosolic calcium ion concentration; • JAK-STAT cascade; • tyrosine phosphorylation of STAT protein; • STAT protein import into nucleus; • mesoderm development; • blood coagulation; • positive regulation of cell proliferation; • negative regulation of cell proliferation; • intrinsic apoptotic signaling pathway in response to oxidative stress; • hormone-mediated signaling pathway; • positive regulation of cell-substrate adhesion; • positive regulation of phosphatidylinositol 3-kinase signaling; • peptidyl-tyrosine phosphorylation; • cytokine-mediated signaling pathway; • negative regulation of cell-cell adhesion; • actin filament polymerization; • cell differentiation; • erythrocyte differentiation; • positive regulation of cell migration; • axon regeneration; • mineralocorticoid receptor signaling pathway; • positive regulation of insulin secretion; • response to lipopolysaccharide; • positive regulation of phosphoprotein phosphatase activity; • positive regulation of interleukin-1 beta production; • positive regulation of tumor necrosis factor production; • positive regulation of protein import into nucleus, translocation; • response to hydroperoxide; • tumor necrosis factor-mediated signaling pathway; • host programmed cell death induced by symbiont; • response to tumor necrosis factor; • histone H3-Y41 phosphorylation; • intracellular signal transduction; • interleukin-12-mediated signaling pathway; • tyrosine phosphorylation of Stat3 protein; • tyrosine phosphorylation of Stat5 protein; • tyrosine phosphorylation of Stat1 protein; • positive regulation of tyrosine phosphorylation of Stat3 protein; • positive regulation of tyrosine phosphorylation of Stat5 protein; • activation of JAK2 kinase activity; • positive regulation of apoptotic process; • positive regulation of DNA binding; • negative regulation of DNA binding; • negative regulation of neuron apoptotic process; • positive regulation of nitric oxide biosynthetic process; • positive regulation of cell differentiation; • negative regulation of heart contraction; • response to antibiotic; • protein autophosphorylation; • platelet-derived growth factor receptor signaling pathway; • regulation of inflammatory response; • positive regulation of inflammatory response; • positive regulation of peptidyl-tyrosine phosphorylation; • positive regulation of cell activation; • positive regulation of sequence-specific DNA binding transcription factor activity; • positive regulation of nitric-oxide synthase biosynthetic process; • interferon-gamma-mediated signaling pathway; • regulation of interferon-gamma-mediated signaling pathway; • growth hormone receptor signaling pathway; • JAK-STAT cascade involved in growth hormone signaling pathway; • positive regulation of growth hormone receptor signaling pathway; • mammary gland epithelium development; • response to interleukin-12; • extrinsic apoptotic signaling pathway; • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; • positive regulation of apoptotic signaling pathway;
	Sources: Amigo / QuickGO
Orthologs
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　　[★] キナーゼカイネースリン酸化酵素 phosphoenzyme phosphotransferase 　

「janus」

　　[★]

n.

ヤーヌス、ヤヌス

[pmid9626554-1] Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (1998). "Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice". Endocr. Rev. 19 (3): 225–68. doi:10.1210/er.19.3.225. PMID 9626554.

[pmid17919086-2] Morgan KJ, Gilliland DG (2008). "A role for JAK2 mutations in myeloproliferative diseases". Annu. Rev. Med. 59: 213–22. doi:10.1146/annurev.med.59.061506.154159. PMID 17919086.

[pmid9590174-3] 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.

[OrthoMaM-4] "OrthoMaM phylogenetic marker: JAK2 coding sequence".

[pmid9360930-5] 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.

[pmid15805263-6] 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.

[pmid15858187-7] 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.

[pmid23942095-8] Gu L, Liao Z, Hoang DT, Dagvadorj A, Gupta S, Blackmon S, Ellsworth E, Talati P, Leiby B, Zinda M, Lallas CD, Trabulsi EJ, McCue P, Gomella L, Huszar D, Nevalainen MT (October 2013). "Pharmacologic Inhibition of Jak2-Stat5 Signaling By Jak2 Inhibitor AZD1480 Potently Suppresses Growth of Both Primary and Castrate-Resistant Prostate Cancer". Clin. Cancer Res. 19 (20): 5658–74. doi:10.1158/1078-0432.CCR-13-0422. PMID 23942095.

[pmid21674578-9] Scott LM (2011). "The JAK2 exon 12 mutations: a comprehensive review". Am. J. Hematol. 86 (8): 668–76. doi:10.1002/ajh.22063. PMID 21674578.

[pmid11679576-10] Sarkar S, Pollack BP, Lin KT, Kotenko SV, Cook JR, Lewis A, Pestka S (2001). "hTid-1, a human DnaJ protein, modulates the interferon signaling pathway". J. Biol. Chem. 276 (52): 49034–42. doi:10.1074/jbc.M103683200. PMID 11679576.

[pmid10358079-11] Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE (1999). "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases". J. Biol. Chem. 274 (24): 17209–18. doi:10.1074/jbc.274.24.17209. PMID 10358079.

[pmid11779507-12] Huang LJ, Constantinescu SN, Lodish HF (2001). "The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor". Mol. Cell 8 (6): 1327–38. doi:10.1016/S1097-2765(01)00401-4. PMID 11779507.

[pmid8343951-13] Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN (1993). "JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin". Cell 74 (2): 227–36. doi:10.1016/0092-8674(93)90414-L. PMID 8343951.

[pmid10551884-14] Sayeski PP, Ali MS, Safavi A, Lyles M, Kim SO, Frank SJ, Bernstein KE (1999). "A catalytically active Jak2 is required for the angiotensin II-dependent activation of Fyn". J. Biol. Chem. 274 (46): 33131–42. doi:10.1074/jbc.274.46.33131. PMID 10551884.

[pmid7500025-15] Chauhan D, Kharbanda SM, Ogata A, Urashima M, Frank D, Malik N, Kufe DW, Anderson KC (1995). "Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells". J. Exp. Med. 182 (6): 1801–6. doi:10.1084/jem.182.6.1801. PMC 2192257. PMID 7500025.

[pmid8536716-16] Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (1995). "Involvement of Janus kinases in the insulin signaling pathway". Eur. J. Biochem. 234 (2): 656–60. doi:10.1111/j.1432-1033.1995.656_b.x. PMID 8536716.

[pmid7540178-17] Frank SJ, Yi W, Zhao Y, Goldsmith JF, Gilliland G, Jiang J, Sakai I, Kraft AS (1995). "Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor". J. Biol. Chem. 270 (24): 14776–85. doi:10.1074/jbc.270.24.14776. PMID 7540178.

[pmid8063815-18] VanderKuur JA, Wang X, Zhang L, Campbell GS, Allevato G, Billestrup N, Norstedt G, Carter-Su C (1994). "Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase". J. Biol. Chem. 269 (34): 21709–17. PMID 8063815.

[pmid10502458-19] Hellgren G, Jansson JO, Carlsson LM, Carlsson B (1999). "The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver". Growth Horm. IGF Res. 9 (3): 212–8. doi:10.1054/ghir.1999.0111. PMID 10502458.

[pmid9492017-20] Gual P, Baron V, Lequoy V, Van Obberghen E (1998). "Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor". Endocrinology 139 (3): 884–93. doi:10.1210/endo.139.3.5829. PMID 9492017.

[pmid11208867-21] Kawazoe Y, Naka T, Fujimoto M, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T (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. 193 (2): 263–9. doi:10.1084/jem.193.2.263. PMC 2193341. PMID 11208867.

[pmid10198225-22] Yamamoto K, Shibata F, Miura O, Kamiyama R, Hirosawa S, Miyasaka N (1999). "Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus". Biochem. Biophys. Res. Commun. 257 (2): 400–4. doi:10.1006/bbrc.1999.0479. PMID 10198225.

[pmid9516124-23] Ogata N, Kouro T, Yamada A, Koike M, Hanai N, Ishikawa T, Takatsu K (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 91 (7): 2264–71. PMID 9516124.

[pmid8702385-24] Fuhrer DK, Yang YC (1996). "Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11". Biochem. Biophys. Res. Commun. 224 (2): 289–96. doi:10.1006/bbrc.1996.1023. PMID 8702385.

[pmid9553131-25] Zhu T, Goh EL, Lobie PE (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. 273 (17): 10682–9. doi:10.1074/jbc.273.17.10682. PMID 9553131.

[pmid10925297-26] Ryu H, Lee JH, Kim KS, Jeong SM, Kim PH, Chung HT (2000). "Regulation of neutrophil adhesion by pituitary growth hormone accompanies tyrosine phosphorylation of Jak2, p125FAK, and paxillin". J. Immunol. 165 (4): 2116–23. doi:10.4049/jimmunol.165.4.2116. PMID 10925297.

[pmid8995399-27] Yin T, Shen R, Feng GS, Yang YC (1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases". J. Biol. Chem. 272 (2): 1032–7. doi:10.1074/jbc.272.2.1032. PMID 8995399.

[pmid8639815-28] Tauchi T, Damen JE, Toyama K, Feng GS, Broxmeyer HE, Krystal G (1996). "Tyrosine 425 within the activated erythropoietin receptor binds Syp, reduces the erythropoietin required for Syp tyrosine phosphorylation, and promotes mitogenesis". Blood 87 (11): 4495–501. PMID 8639815.

[pmid8912646-29] Maegawa H, Kashiwagi A, Fujita T, Ugi S, Hasegawa M, Obata T, Nishio Y, Kojima H, Hidaka H, Kikkawa R (1996). "SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates". Biochem. Biophys. Res. Commun. 228 (1): 122–7. doi:10.1006/bbrc.1996.1626. PMID 8912646.

[pmid8943354-30] Jiao H, Berrada K, Yang W, Tabrizi M, Platanias LC, Yi T (1996). "Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1". Mol. Cell. Biol. 16 (12): 6985–92. PMC 231702. PMID 8943354.

[pmid10772872-31] Wu DW, Stark KC, Dunnington D, Dillon SB, Yi T, Jones C, Pelus LM (2000). "SH2-Containing protein tyrosine phosphatase-1 (SHP-1) association with Jak2 in UT-7/Epo cells". Blood Cells Mol. Dis. 26 (1): 15–24. doi:10.1006/bcmd.2000.0273. PMID 10772872.

[pmid10531356-32] Pollack BP, Kotenko SV, He W, Izotova LS, Barnoski BL, Pestka S (1999). "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity". J. Biol. Chem. 274 (44): 31531–42. doi:10.1074/jbc.274.44.31531. PMID 10531356.

[pmid9343427-33] Rui L, Mathews LS, Hotta K, Gustafson TA, Carter-Su C (1997). "Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling". Mol. Cell. Biol. 17 (11): 6633–44. PMC 232517. PMID 9343427.

[pmid12370803-34] Xie S, Lin H, Sun T, Arlinghaus RB (2002). "Jak2 is involved in c-Myc induction by Bcr-Abl". Oncogene 21 (47): 7137–46. doi:10.1038/sj.onc.1205942. PMID 12370803.

[pmid7535773-35] VanderKuur J, Allevato G, Billestrup N, Norstedt G, Carter-Su C (1995). "Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2". J. Biol. Chem. 270 (13): 7587–93. doi:10.1074/jbc.270.13.7587. PMID 7535773.

[pmid9126968-36] Giordano V, De Falco G, Chiari R, Quinto I, Pelicci PG, Bartholomew L, Delmastro P, Gadina M, Scala G (1997). "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. 158 (9): 4097–103. PMID 9126968.

[pmid10882725-37] Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A (2000). "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2". J. Biol. Chem. 275 (38): 29338–47. doi:10.1074/jbc.M003456200. PMID 10882725.

[pmid10421843-38] Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A (1999). "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes Cells 4 (6): 339–51. doi:10.1046/j.1365-2443.1999.00263.x. PMID 10421843.

[pmid9344848-39] 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 (1997). "Cloning and characterization of novel CIS family genes". Biochem. Biophys. Res. Commun. 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID 9344848.

[pmid9575217-40] Barahmand-Pour F, Meinke A, Groner B, Decker T (1998). "Jak2-Stat5 interactions analyzed in yeast". J. Biol. Chem. 273 (20): 12567–75. doi:10.1074/jbc.273.20.12567. PMID 9575217.

[pmid9047382-41] Fujitani Y, Hibi M, Fukada T, Takahashi-Tezuka M, Yoshida H, Yamaguchi T, Sugiyama K, Yamanaka Y, Nakajima K, Hirano T (1997). "An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT". Oncogene 14 (7): 751–61. doi:10.1038/sj.onc.1200907. PMID 9047382.

[pmid9133424-42] Takeshita T, Arita T, Higuchi M, Asao H, Endo K, Kuroda H, Tanaka N, Murata K, Ishii N, Sugamura K (1997). "STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction". Immunity 6 (4): 449–57. doi:10.1016/S1074-7613(00)80288-5. PMID 9133424.

[pmid10064597-43] Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". EMBO J. 18 (5): 1309–20. doi:10.1093/emboj/18.5.1309. PMC 1171221. PMID 10064597.

[pmid11713228-44] Dif F, Saunier E, Demeneix B, Kelly PA, Edery M (2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology 142 (12): 5286–93. doi:10.1210/en.142.12.5286. PMID 11713228.

[pmid9202126-45] Endo TA, 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 (1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature 387 (6636): 921–4. doi:10.1038/43213. PMID 9202126.

[pmid10455112-46] Pezet A, Favre H, Kelly PA, Edery M (1999). "Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling". J. Biol. Chem. 274 (35): 24497–502. doi:10.1074/jbc.274.35.24497. PMID 10455112.

[pmid11971965-47] Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O (2002). "Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1". Mol. Cell. Biol. 22 (10): 3316–26. doi:10.1128/MCB.22.10.3316-3326.2002. PMC 133778. PMID 11971965.

[pmid9178903-48] Takahashi-Tezuka M, Hibi M, Fujitani Y, Fukada T, Yamaguchi T, Hirano T (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.

[pmid9473212-49] Yamashita Y, Watanabe S, Miyazato A, Ohya Ki, Ikeda U, Shimada K, Komatsu N, Hatake K, Miura Y, Ozawa K, Mano H (1998). "Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription". Blood 91 (5): 1496–507. PMID 9473212.

[pmid9510175-50] Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB (1998). "Induction of Jak/STAT signaling by activation of the type 1 TNF receptor". J. Immunol. 160 (6): 2742–50. PMID 9510175.

[pmid9162069-51] Shigematsu H, Iwasaki H, Otsuka T, Ohno Y, Arima F, Niho Y (1997). "Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity". J. Biol. Chem. 272 (22): 14334–40. doi:10.1074/jbc.272.22.14334. PMID 9162069.

[pmid7530656-52] "Findings of scientific misconduct". NIH Guide Grants Contracts 24 (42): 1–2. 1995. PMID 7495607.

[pmid20562009-53] 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". Mol. Cell. Endocrinol. 325 (1-2): 143–9. doi:10.1016/j.mce.2010.05.010. PMC 2902710. PMID 20562009.

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案内

Janus kinase 2