Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12-mediated T cell function.
Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNalpha, although a high concentration of IFNalpha can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNalpha-dependent signaling while being required in mediating IL-12-dependent biological responses.
Shimoda
K
K
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. kshimoda@intermed1.med.kyushu-u.ac.jp
Kato
K
K
Aoki
K
K
Matsuda
T
T
Miyamoto
A
A
Shibamori
M
M
Yamashita
M
M
Numata
A
A
Takase
K
K
Kobayashi
S
S
Shibata
S
S
Asano
Y
Y
Gondo
H
H
Sekiguchi
K
K
Nakayama
K
K
Nakayama
T
T
Okamura
T
T
Okamura
S
S
Niho
Y
Y
Nakayama
K
K
D000818:Animals; D004622:Embryo, Mammalian; D018390:Gene Targeting; D016898:Interferon-alpha / Q000502:physiology*; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013234:Stem Cells; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D053634:TYK2 Kinase; D014162:Transfection
D016898:Interferon-alpha; D015850:Interleukin-6; D011506:Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse