Janus kinase
From Wikipedia, the free encyclopedia
Janus kinase (JAK) is a family of intracellular tyrosine kinases, ranging from 120-140 kDa, that are involved in the JAK-STAT pathway. They participate in the signalling cascade of cytokines by associating with one of the cytokine receptors, for example, the interferon receptor.
The kinase was initially named JAK after "just another kinase." Later, it was said to be named after Janus, the Thessalian gatekeeper of heaven worshipped by Romans. He is described as having two faces. The kinase is named after him because it has two phosphate-transferring domains (only one of which has a known biological role).
There are four JAK family members, JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2). Transgenic mice that do not express JAK1 have defective responses to some cytokines such as interferon-gamma <ref>S. Rodig, M. Meraz, J. White, P. Lampe, J. Riley, C. Arthur, K. King, K. Sheehan, L. Yin, D. Pennica, E. Johnson and R. Schreiber (1998) "Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses" in Cell Volume 93, pages 373-383. Entrez PubMed 9590172</ref> JAK1 and JAK2 are involved in type II interferon (interferon-gamma) signalling, whereas JAK1 and TYK2 are involved type I interferon signalling. Mice that do not express TYK2 have defective natural killer cell function<ref>D. Stoiber, B. Kovacic, C. Schuster, C. Schellack, M. Karaghiosoff , R. Kreibich, E. Weisz, M. Artwohl, O. Kleine, M. Muller, S. Baumgartner-Parzer, J. Ghysdael, M. Freissmuth and V. Sexl (2004) "TYK2 is a key regulator of the surveillance of B lymphoid tumors" in Journal of Clinical Investigaion Volume 114, pages 1650-1658. Entrez PubMed 15578097</ref>.
Contents |
[edit] JAK1
| Janus kinase 1 (a protein tyrosine kinase)
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| Identifiers | |
| Symbol(s) | JAK1 JAK1B |
| Entrez | 3716 |
| OMIM | 147795 |
[edit] JAK2
| Janus kinase 2 (a protein tyrosine kinase)
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| Identifiers | |
| Symbol(s) | JAK2 |
| Entrez | 3717 |
| OMIM | 147796 |
Mutation in JAK2 (V617F) has been associated with myeloproliferative disorders, most specifically with polycythemia vera. JAK2 signaling is activated downstream from the prolactin receptor<ref>Christine Bole-Feysot1, Vincent Goffin1, Marc Edery, Nadine Binart and Paul A. Kelly (1998) "Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice" in Endocrine Reviews Volume 19, pages 225-268. Entrez PubMed 9626554</ref>. JAK2 gene fusions with the TEL(ETV6) (TEL-JAK2) and PCM1 genes have been found in leukemia patients.<ref>Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA (1997) "A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia" in Science Volume 278 (5341), pages 1309-12. Entrez PubMed 9360930 </ref><ref>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" in Cancer Res Volume 65 (7), pages 2662-67. Entrez PubMed 15805263 </ref>
[edit] JAK3
| Janus kinase 3 (a protein tyrosine kinase, leukocyte)
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| Identifiers | |
| Symbol(s) | JAK3 |
| Entrez | 3718 |
| OMIM | 600173 |
Mutations of JAK3 result in severe combined immunodeficiency (SCID). Mice that do not express JAK3 have T-cells and B-cells that fail to respond to many cytokines <ref>T. Nosaka, J. van Deursen, R. Tripp, W. Thierfelder, B. Witthuhn, A. McMickle, P. Doherty, G. Grosveld and J. Ihle (1995) "Defective lymphoid development in mice lacking Jak3" in Science Volume 270, pages 800-802. Entrez PubMed 7481769</ref>.
[edit] TYK2
| tyrosine kinase 2
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| Identifiers | |
| Symbol(s) | TYK2 |
| Entrez | 7297 |
| OMIM | 176941 |
[edit] References
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| Cell signaling |
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| Key concepts - Ligand | Receptor | Second messenger | Protein kinase | Transcription factor | Cell signaling networks |
| Pathways - Apoptosis | Ca2+ signaling | Cytokine signaling | Hedgehog | Integrin signaling | JAK/STAT | Lipid signaling | MAPK/ERK pathway | mTOR | NF-kB | Notch | p53 | TGFβ | Wnt |
