Dispensability of Jak1 tyrosine kinase for interleukin-2-induced cell growth signaling in a human T cell line.
The tyrosine kinases Jak1 and Jak3 are known to be associated with the beta and gamma chains of interleukin-2 receptor (IL-2R). They are activated by stimulation with IL-2, IL-4, IL-7, IL-9, or IL-15, receptors of which share the gamma chain of the IL-2R. We have obtained direct evidence of Jak1 association with the alpha chains of receptors for IL-4, IL-7 and IL-9 and with the beta chain of IL-2R, which is also common to the IL-15R. Furthermore, we have prepared mutant IL-2R beta chains with a mutation in the box 1 region, which is conserved among the IL-2R beta chain and the alpha chains of the other cytokine receptors sharing the IL-2R gamma chain. Using MOLT-4 transfectants with the mutant beta chains, we found that two conserved proline residues within the box 1 region are essentially involved in association with Jak1. The MOLT-4 transfectants with the mutant beta chains lacking Jak1 association showed IL-2 responsiveness, in terms of activation of Jak3 and Stat5 and induction of cell growth, indicating that Jak1 is dispensable for IL-2-mediated cell growth signaling and that Jak1 activation is not required for activation of Jak3 and Stat5 in the MOLT-4 transfectants.
Higuchi
M
M
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.
Asao
H
H
Tanaka
N
N
Oda
K
K
Takeshita
T
T
Nakamura
M
M
Van Snick
J
J
Sugamura
K
K
D015703:Antigens, CD / Q000502:physiology; D001483:Base Sequence; D002455:Cell Division; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D008894:Milk Proteins; D008969:Molecular Sequence Data; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology; D019948:Receptors, Interleukin-4; D020395:Receptors, Interleukin-7; D053651:Receptors, Interleukin-9; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C508045:IL9R protein, human; D007376:Interleukin-2; D008894:Milk Proteins; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D020395:Receptors, Interleukin-7; D053651:Receptors, Interleukin-9; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3