Reference : Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytok...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/16408
Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptors
English
Haan, Claude mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Rolvering, Catherine mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Raulf, F. [Autoimmunity, Transplantation, and Inflammation, Novartis Institute for Biomedical Research, Basel CH-4056, Switzerland]
Kapp, M. [Autoimmunity, Transplantation, and Inflammation, Novartis Institute for Biomedical Research, Basel CH-4056, Switzerland]
Drückes, P. [Expertise Platform Kinases, Novartis Institute for Biomedical Research, Basel CH-4056, Switzerland]
Thoma, G. [Global Discovery Chemistry, Novartis Institute for Biomedical Research, Basel CH-4056, Switzerland]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Zerwes, H.-G. [Autoimmunity, Transplantation, and Inflammation, Novartis Institute for Biomedical Research, Basel CH-4056, Switzerland]
2011
Chemistry & Biology
Current Biology
18
3
314-323
Yes (verified by ORBilu)
International
1074-5521
London
United Kingdom
[en] cytokine receptor; interleukin 2; Janus kinase 1; Janus kinase 3; protein kinase inhibitor; small interfering RNA; STAT5 protein ; animal; article; cell line; chemistry; drug antagonism; genetics; human; metabolism; mouse; mutation; phosphorylation; RNA interference; signal transduction ; Animals; Cell Line; Humans; Interleukin-2; Janus Kinase 1; Janus Kinase 3; Mice; Mutation; Phosphorylation; Protein Kinase Inhibitors; Receptors ; Cytokine; RNA Interference; RNA ; Small Interfering; Signal Transduction; STAT5 Transcription Factor
[en] Genetic deficiency of Jak3 leads to abrogation of signal transduction through the common gamma chain (γc) and thus to immunodeficiency suggesting that specific inhibition of Jak3 kinase may result in immunosuppression. Jak1 cooperates with Jak3 in signaling through γc-containing receptors. Unexpectedly, a Jak3-selective inhibitor was less efficient in abolishing STAT5 phosphorylation than pan-Jak inhibitors. We therefore explored the roles of Jak1 and Jak3 kinase functionality in signaling using a reconstituted system. The presence of kinase-inactive Jak1 but not kinase-inactive Jak3 resulted in complete abolishment of STAT5 phosphorylation. Specific inhibition of the "analog-sensitive" mutant AS-Jak1 but not AS-Jak3 by the ATP-competitive analog 1NM-PP1 abrogated IL-2 signaling, corroborating the data with the selective Jak3 inhibitor. Jak1 thus plays a dominant role over Jak3 and these data challenge the notion that selective ATP-competitive Jak3 kinase inhibitors will be effective. © 2011 Elsevier Ltd.
http://hdl.handle.net/10993/16408
10.1016/j.chembiol.2011.01.012
http://www.scopus.com/inward/record.url?eid=2-s2.0-79953043687&partnerID=40&md5=16c3c37f262826ec72ac3fd6e9e8c39b
cited By (since 1996)18
Scopus

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