Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells.
Many cytokines function through interaction with receptors of the cytokine receptor superfamily. Although lacking catalytic domains, cytokine receptors couple ligand binding to induction of protein tyrosine phosphorylation. Recent studies have shown that one or more of the Janus kinase family members (Jaks) associate with cytokine receptors and are tyrosine phosphorylated and activated following ligand binding. Here we describe a new Jak family kinase, Jak-3, and demonstrate that Jak-3, and to a lesser extent Jak-1, are tyrosine phosphorylated and Jak-3 is activated in the responses to interleukin-2 and interleukin-4 in T cells and myeloid cells. Jak-3 activation requires the serine-rich, membrane-proximal domain of the interleukin-2 receptor beta-chain, but does not require the acidic domain that is required for association and activation of Src family kinases.
Department of Biochemistry, St Jude Children's Research Hospital, Memphis, Tennessee 38105.
B A
BA
Witthuhn
O
O
Silvennoinen
O
O
Miura
K S
KS
Lai
C
C
Cwik
E T
ET
Liu
J N
JN
Ihle
D000595:Amino Acid Sequence; D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells; D002460:Cell Line; D016207:Cytokines / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D053616:Janus Kinase 3; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*
D016207:Cytokines; D007376:Interleukin-2; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3