Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway (original) (raw)
- Tadaaki Miyazaki,
- Akinori Takaoka,
- Leonor Nogueira,
- Ivan Dikic,
- Hodaka Fujii,
- Shiho Tsujino,
- Yukiko Mitani,
- Michiyuki Maeda,
- Joseph Schlessinger, and
- Tadatsugu Taniguchi
- Department of Immunology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113, Japan; Department of Pharmacology, New York University Medical Center, New York, New York 10016 USA; Chest Disease Research Institute, Kyoto University, Sakyo-ku, Kyoto, 606-01, Japan
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.
Footnotes
↵Corresponding author.
E-MAIL tada{at}m.u-tokyo.ac.jp; FAX 81-3-5689-7214.
- Received December 3, 1997.
- Accepted January 28, 1998.
Cold Spring Harbor Laboratory Press