Cutting edge: tyk2 is required for the induction and nuclear translocation of Daxx which regulates IFN-alpha-induced suppression of B lymphocyte formation.
IFN-alpha inhibits B lymphocyte development, and the nuclear protein Daxx has been reported to be essential for this biological activity. We show in this study that IFN-alpha inhibits the clonal proliferation of B lymphocyte progenitors in response to IL-7 in wild-type, but not in tyk2-deficient, mice. In addition, the IFN-alpha-induced up-regulation and nuclear translocation of Daxx are completely abrogated in the absence of tyk2. Therefore, tyk2 is directly involved in IFN-alpha signaling for the induction and translocation of Daxx, which may result in B lymphocyte growth arrest and/or apoptosis.
Shimoda
Kazuya
K
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. kshimoda@intmed1.med.kyushu-u.ac.jp
Kamesaki
Kenjirou
K
Numata
Akihiko
A
Aoki
Kenichi
K
Matsuda
Tadashi
T
Oritani
Kenji
K
Tamiya
Sadafumi
S
Kato
Kouji
K
Takase
Ken
K
Imamura
Rie
R
Yamamoto
Tetsuya
T
Miyamoto
Toshihiro
T
Nagafuji
Koji
K
Gondo
Hisashi
H
Nagafuchi
Seiho
S
Nakayama
Kei-Ichi
K
Harada
Mine
M
D021581:Active Transport, Cell Nucleus / Q000235:genetics / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D018920:Coculture Techniques; D006131:Growth Inhibitors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016898:Interferon-alpha / Q000502:physiology*; D015851:Interleukin-7 / Q000037:antagonists & inhibitors / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D053634:TYK2 Kinase
D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D015851:Interleukin-7; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D011506:Proteins; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse