title: Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway.
abstract: 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.
authors.affiliation: Department of Immunology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miyazaki
authors.forename: A
authors.initials: A
authors.lastname: Takaoka
authors.forename: L
authors.initials: L
authors.lastname: Nogueira
authors.forename: I
authors.initials: I
authors.lastname: Dikic
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: S
authors.initials: S
authors.lastname: Tsujino
authors.forename: Y
authors.initials: Y
authors.lastname: Mitani
authors.forename: M
authors.initials: M
authors.lastname: Maeda
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: 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
chemical_list: 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