Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway (original) (raw)

  1. Tadaaki Miyazaki,
  2. Akinori Takaoka,
  3. Leonor Nogueira,
  4. Ivan Dikic,
  5. Hodaka Fujii,
  6. Shiho Tsujino,
  7. Yukiko Mitani,
  8. Michiyuki Maeda,
  9. Joseph Schlessinger, and
  10. Tadatsugu Taniguchi
  11. 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