The Janus kinases (Jaks)

Firmbach-Kraft I, Byers M, Shows T, Dalla-Favera R, Krolewski JJ: Tyk2, prototype of a novel class of non-receptor tyrosine kinase genes. Oncogene. 1990, 5: 1329-1336. This paper and [2-6] were the first studies to report the cloning of Jaks Wilks AF: Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction. Proc Natl Acad Sci USA. 1989, 86: 1603-1607. See [1] Wilks AF: Cloning members of protein-tyrosine kinase family using polymerase chain reaction. Methods Enzymol. 1991, 200: 533-546. See [1] Harpur AG, Andres AC, Ziemiecki A, Aston RR, Wilks AF: JAK2, a third member of the JAK family of protein tyrosine kinases. Oncogene. 1992, 7: 1347-1353. See [1] Krolewski JJ, Lee R, Eddy R, Shows TB, Dalla-Favera R: Identification and chromosomal mapping of new human tyrosine kinase genes. Oncogene. 1990, 5: 277-282. See [1] Kawamura M, McVicar DW, Johnston JA, Blake TB, Chen YQ, Lal BK, Lloyd AR, Kelvin DJ, Staples JE, Ortaldo JR, et al: Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. Proc Natl Acad Sci USA. 1994, 91: 6374-6378. See [1] Perrimon N, Mahowald AP: I(1)hopscotch, a larval-pupal zygotic lethal with a specific maternal effect on segmentation in Drosophila. Dev Biol. 1986, 118: 28-41. 10.1016/0012-1606(86)90070-9. This paper and [8] report the first identification of the Drosophila Jak Binari R, Perrimon N: Stripe-specific regulation of pair-rule genes by hopscotch, a putative Jak family tyrosine kinase in Drosophila. Genes Dev. 1994, 8: 300-312. See [7] Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S: The protein kinase complement of the human genome. Science. 2002, 298: 1912-1934. 10.1126/science.1075762. An excellent discussion of the all the kinases present in the human genome Chen M, Cheng A, Candotti F, Zhou YJ, Hymel A, Fasth A, Notarangelo LD, O'Shea JJ: Complex effects of naturally occurring mutations in the JAK3 pseudokinase domain: evidence for interactions between the kinase and pseudokinase domains. Mol Cell Biol. 2000, 20: 947-956. 10.1128/MCB.20.3.947-956.2000. This paper and [11-15] report analyses of the function of the Jak pseudokinase domain Saharinen P, Takaluoma K, Silvennoinen O: Regulation of the Jak2 tyrosine kinase by its pseudokinase domain. Mol Cell Biol. 2000, 20: 3387-3395. 10.1128/MCB.20.10.3387-3395.2000. See [10] Hanratty WP, Dearolf CR: The Drosophila Tumorous-lethal hematopoietic oncogene is a dominant mutation in the hopscotch locus. Mol Gen Genet. 1993, 238: 33-37. See [10] Jinks TM, Polydorides AD, Calhoun G, Schedl P: The JAK/STAT signaling pathway is required for the initial choice of sexual identity in Drosophila melanogaster. Mol Cell. 2000, 5: 581-587. 10.1016/S1097-2765(00)80451-7. See [10] Johansen KA, Iwaki DD, Lengyel JA: Localized JAK/STAT signaling is required for oriented cell rearrangement in a tubular epithelium. Development. 2003, 130: 135-145. 10.1242/dev.00202. See [10] Saharinen P, Silvennoinen O: The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction. J Biol Chem. 2002, 277: 47954-47963. 10.1074/jbc.M205156200. See [10] Velazquez L, Fellous M, Stark GR, Pellegrini S: A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell. 1992, 70: 313-322. 10.1016/0092-8674(92)90105-L. The first evidence that Jaks are critical for cytokine signaling. The study also indicates that Jaks may regulate cytokine receptor expression Huang LJ, Constantinescu SN, Lodish HF: The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor. Mol Cell. 2001, 8: 1327-1338. 10.1016/S1097-2765(01)00401-4. Further support for a role of Jaks in regulating intracellular trafficking of cytokine receptors Zhou YJ, Chen M, Cusack NA, Kimmel LH, Magnuson KS, Boyd JG, Lin W, Roberts JL, Lengi A, Buckley RH, et al: Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases. Mol Cell. 2001, 8: 959-969. 10.1016/S1097-2765(01)00398-7. Evidence that the Jak FERM domain has two important functions: mediating receptor association and regulating kinase activity Musso T, Johnston JA, Linnekin D, Varesio L, Rowe TK, O'Shea JJ, McVicar DW: Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7. J Exp Med. 1995, 181: 1425-1431. 10.1084/jem.181.4.1425. This article and [20] demonstrate the tissue-specific and activation-dependent expression of Jak3 Tortolani PJ, Lal BK, Riva A, Johnston JA, Chen YQ, Reaman GH, Beckwith M, Longo D, Ortaldo JR, Bhatia K, et al: Regulation of JAK3 expression and activation in human B cells and B cell malignancies. J Immunol. 1995, 155: 5220-5226. See [19] Hofmann SR, Lam AQ, Frank S, Zhou YJ, Ramos HL, Kanno Y, Agnello D, Youle RJ, O'Shea JJ: Jak3-independent trafficking of the common gamma chain receptor subunit: chaperone function of Jaks revisited. Mol Cell Biol. 2004, 24: 5039-5049. 10.1128/MCB.24.11.5039-5049.2004. This paper and [22] present analyses of the intracellular trafficking of Jaks and their cognate receptors Ragimbeau J, Dondi E, Alcover A, Eid P, Uze G, Pellegrini S: The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression. EMBO J. 2003, 22: 537-547. 10.1093/emboj/cdg038. See [21] Argetsinger LS, Campbell GS, Yang X, Witthuhn BA, Silvennoinen O, Ihle JN, Carter-Su C: Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell. 1993, 74: 237-244. 10.1016/0092-8674(93)90415-M. This paper and [24-26] are the studies that first demonstrated that cytokine receptors couple to Janus kinases Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN: JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 1993, 74: 227-236. 10.1016/0092-8674(93)90414-L. See [23] Muller M, Briscoe J, Laxton C, Guschin D, Ziemiecki A, Silvennoinen O, Harpur AG, Barbieri G, Witthuhn BA, Schindler C, et al: The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. Nature. 1993, 366: 129-135. 10.1038/366129a0. See [23] Silvennoinen O, Ihle JN, Schlessinger J, Levy DE: Interferon-induced nuclear signalling by Jak protein tyrosine kinases. Nature. 1993, 366: 583-585. 10.1038/366583a0. See [23] Shimoda K, Kato K, Aoki K, Matsuda T, Miyamoto A, Shibamori M, Yamashita M, Numata A, Takase K, Kobayashi S, et al: Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12-mediated T cell function. Immunity. 2000, 13: 561-571. 10.1016/S1074-7613(00)00055-8. This report and [28,29] on the generation of Tyk2 knockout mice reveal its restricted role Karaghiosoff M, Neubauer H, Lassnig C, Kovarik P, Schindler H, Pircher H, McCoy B, Bogdan C, Decker T, Brem G, et al: Partial impairment of cytokine responses in Tyk2-deficient mice. Immunity. 2000, 13: 549-560. 10.1016/S1074-7613(00)00054-6. See [27] Karaghiosoff M, Steinborn R, Kovarik P, Kriegshauser G, Baccarini M, Donabauer B, Reichart U, Kolbe T, Bogdan C, Leanderson T, et al: Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat Immunol. 2003, 4: 471-477. 10.1038/ni910. See [27] Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, King KL, Sheehan KC, Yin L, Pennica D, et al: Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell. 1998, 93: 373-383. 10.1016/S0092-8674(00)81166-6. A description of the Jak1 knockout mice and its essential roles in cytokine signaling Neubauer H, Cumano A, Muller M, Wu H, Huffstadt U, Pfeffer K: Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell. 1998, 93: 397-409. 10.1016/S0092-8674(00)81168-X. This paper and [32] describe the embryonic lethality associated with Jak2 deficiency Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, Vanin EF, Bodner S, Colamonici OR, van Deursen JM, et al: Jak2 is essential for signaling through a variety of cytokine receptors. Cell. 1998, 93: 385-395. 10.1016/S0092-8674(00)81167-8. See [31] Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnston JA, Candotti F, O'Shea JJ, et al: Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature. 1995, 377: 65-68. 10.1038/377065a0. This paper and [34] report the first identification of humans with Jak mutations, which result in severe combined immunodeficiency Russell SM, Tayebi N, Nakajima H, Riedy MC, Roberts JL, Aman MJ, Migone TS, Noguchi M, Markert ML, Buckley RH, et al: Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science. 1995, 270: 797-800. See [33] O'Shea JJ, Pesu M, Borie DC, Changelian PS: A new modality for immunosuppression: targeting the JAK/STAT pathway. Nat Rev Drug Discov. 2004, 3: 555-564. 10.1038/nrd1441. A comprehensive review of Jak3 antagonists Nosaka T, van Deursen JM, Tripp RA, Thierfelder WE, Witthuhn BA, McMickle AP, Doherty PC, Grosveld GC, Ihle JN: Defective lymphoid development in mice lacking Jak3. Science. 1995, 270: 800-802. This paper and [37,38] are the first reports of Jak3 knockout mice and their resultant immunodeficiency Park SY, Saijo K, Takahashi T, Osawa M, Arase H, Hirayama N, Miyake K, Nakauchi H, Shirasawa T, Saito T: Developmental defects of lymphoid cells in Jak3 kinase-deficient mice. Immunity. 1995, 3: 771-782. 10.1016/1074-7613(95)90066-7. See [36] Thomis DC, Gurniak CB, Tivol E, Sharpe AH, Berg LJ: Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3. Science. 1995, 270: 794-797. See [36] Sorrentino RP, Melk JP, Govind S: Genetic analysis of contributions of dorsal group and JAK-Stat92E pathway genes to larval hemocyte concentration and the egg encapsulation response in Drosophila. Genetics. 2004, 166: 1343-1356. 10.1534/genetics.166.3.1343. This paper and [40-45] give evidence for the broad functions of the Jak/Stat pathway in regulating insect development Luo H, Asha H, Kockel L, Parke T, Mlodzik M, Dearolf CR: The Drosophila Jak kinase hopscotch is required for multiple developmental processes in the eye. Dev Biol. 1999, 213: 432-441. 10.1006/dbio.1999.9390. See [39] Callus BA, Mathey-Prevot B: SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc. Oncogene. 2002, 21: 4812-4821. 10.1038/sj.onc.1205618. See [39] Chen X, Oh SW, Zheng Z, Chen HW, Shin HH, Hou SX: Cyclin D-Cdk4 and cyclin E-Cdk2 regulate the Jak/STAT signal trans-duction pathway in Drosophila. Dev Cell. 2003, 4: 179-190. 10.1016/S1534-5807(03)00024-8. See [39] O'Shea JJ, Gadina M, Schreiber RD: Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell. 2002, 109 (Suppl): S121-S131. 10.1016/S0092-8674(02)00701-8. See [39] Hombria JC, Brown S: The fertile field of Drosophila Jak/STAT signalling. Curr Biol. 2002, 12: R569-R575. 10.1016/S0960-9822(02)01057-6. See [39] Harrison DA, Binari R, Nahreini TS, Gilman M, Perrimon N: Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. EMBO J. 1995, 14: 2857-2865. See [39] Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P: 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. 1997, 90: 2535-2540. This article and [47-49] give support for the role of Jaks in malignant transformation Cools J, Peeters P, Voet T, Aventin A, Mecucci C, Grandchamp B, Marynen P: Genomic organization of human JAK2 and mutation analysis of its JH2-domain in leukemia. Cytogenet Cell Genet. 1999, 85: 260-266. 10.1159/000015308. See [46] Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA: A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science. 1997, 278: 1309-1312. 10.1126/science.278.5341.1309. See [46] Migone TS, Lin JX, Cereseto A, Mulloy JC, O'Shea JJ, Franchini G, Leonard WJ: Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I. Science. 1995, 269: 79-81. See [46] Zhou YJ, Hanson EP, Chen YQ, Magnuson K, Chen M, Swann PG, Wange RL, Changelian PS, O'Shea JJ: Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity. Proc Natl Acad Sci USA. 1997, 94: 13850-13855. 10.1073/pnas.94.25.13850. This study and [51,52] describe the functional significance of Jak autophosphorylation Kurzer JH, Argetsinger LS, Zhou YJ, Kouadio JL, O'Shea JJ, Carter-Su C: Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation of JAK2 by SH2-B beta. Mol Cell Biol. 2004, 24: 4557-4570. 10.1128/MCB.24.10.4557-4570.2004. See [50] Feener EP, Rosario F, Dunn SL, Stancheva Z, Myers MG: Tyrosine phosphorylation of Jak2 in the JH2 domain inhibits cytokine signaling. Mol Cell Biol. 2004, 24: 4968-4978. 10.1128/MCB.24.11.4968-4978.2004. See [50] Kamakura S, Oishi K, Yoshimatsu T, Nakafuku M, Masuyama N, Gotoh Y: Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling. Nat Cell Biol. 2004, 6: 547-554. 10.1038/ncb1138. This paper and [54,55] provide emerging evidence of cross-talk between the Jak/Stat pathway and other signaling pathways Josten F, Fuss B, Feix M, Meissner T, Hoch M: Cooperation of JAK/STAT and Notch signaling in the Drosophila foregut. Dev Biol. 2004, 267: 181-189. 10.1016/j.ydbio.2003.11.016. See [53] Bach EA, Vincent S, Zeidler MP, Perrimon N: A sensitized genetic screen to identify novel regulators and components of the Drosophila Janus kinase/signal transducer and activator of transcription pathway. Genetics. 2003, 165: 1149-1166. See [53] Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, Rizzuti BJ, Sawyer PS, Perry BD, Brissette WH, et al: Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science. 2003, 302: 875-878. 10.1126/science.1087061. A report of the first Jak inhibitor, which is efficacious as an immunosuppressant in a primate model of transplant rejection