Regulation of IL-2 signaling.
Several tyrosine kinases such as Jak1, Jak3, Lck and Syk are known to participate in IL-2-mediated intracellular signal transduction. Jak1, Lck and Syk are associated with the cytoplasmic domain of the beta chain, whereas Jak3 is associated with the cytoplasmic domain of the gamma chain, which is shared among receptors for IL-2, IL-4, IL-7 and IL-15. We first demonstrated that Jak1 is associated with the alpha chains of receptors for IL-4, IL-7 and IL-15 as well as the IL-2 receptor beta chain. Furthermore, we revealed that two proline residues in the box1 region, which is conserved in the IL-2 receptor beta chain and the alpha chains of the cytokine receptors, are essentially involved in association with Jak1. The MOLT4 transfectants with the box1 mutants of the IL-2 receptor beta chain lacking Jak1 association showed IL-2 responsiveness, in terms of activations 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 MOLT4 transfectants.
Higuchi
M
M
Asao
H
H
Tanaka
N
N
Oda
K
K
Takeshita
T
T
Sugamura
K
K
D000595:Amino Acid Sequence; D002460:Cell Line; D017124:Conserved Sequence; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism
D004792:Enzyme Precursors; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C000606896:SYK protein, human; D000072377:Syk Kinase; D019061:src-Family Kinases