Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway.
Many cytokines transmit signals to the cell interior through activation of receptor-associated, Janus family protein tyrosine kinases (Jak PTKs). The interleukin-2 receptor (IL-2R) is associated with the Jak1 and Jak3 PTKs, and ligand-induced activation of these PTKs is essential for lymphocyte proliferation. Here, the nonreceptor PTK, Pyk2, was found to be activated following IL-2 stimulation in a Jak-dependent manner. Furthermore, physical association was detected between endogenous Pyk2 and Jak3, and a dominant interfering mutant of Pyk2 inhibited IL-2-induced cell proliferation without affecting Stat5 activation. Collectively, these results suggest that Pyk2 is a newly identified component of the Jak-mediated IL-2 signaling pathway.
Miyazaki
T
T
Department of Immunology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113, Japan.
Takaoka
A
A
Nogueira
L
L
Dikic
I
I
Fujii
H
H
Tsujino
S
S
Mitani
Y
Y
Maeda
M
M
Schlessinger
J
J
Taniguchi
T
T
D001665:Binding Sites / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D051418:Focal Adhesion Kinase 2; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D053616:Janus Kinase 3; D008894:Milk Proteins; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000187:drug effects
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008894:Milk Proteins; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C507933:JAK3 protein, human; D053616:Janus Kinase 3