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Published online before print December 22, 2009
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0409227


Revised October 20, 2009.
Accepted for publication November 16, 2009.

Article

The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems

Michaela Collins *, Mikaela Tremblay *, Nicole Chapman {dagger}, Miranda Curtiss {dagger}, Paul B. Rothman {dagger}{ddagger}, and Jon C. D. Houtman *{dagger}@

Departments of *Microbiology and{ddagger}Internal Medicine and{dagger}Immunology Graduate Program, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

@ To whom correspondence should be addressed. E-mail: jon-houtman{at}uiowa.edu.


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Abstract

The tyrosine kinase Pyk2 is vital for integrating receptor-mediated signals controlling adhesion and motility in neuronal, epithelial, and hematopoietic cell types. In T cells, the stimulation of the TCR and costimulatory, chemokine, cytokine, and integrin receptors leads to the phosphorylation of Pyk2 and the induction of its catalytic activity. However, our understanding of the mechanism of the TCR-induced, site-specific phosphorylation of this kinase is incomplete and contradictory. To address this issue, the role of individual signaling pathways in the phosphorylation of Pyk2 tyrosines 402 and 580 upon TCR activation was assessed in human T cells. In contrast to other receptor systems, the TCR-induced phosphorylation of Pyk2 tyrosines 402 and 580 was dependent on the Src family kinases, Fyn or Lck. Interestingly, the TCR-mediated phosphorylation of Pyk2 tyrosines 402 and 580 did not require Ca2+ influx, ZAP-70 activation, actin cytoskeleton rearrangement, or PI3K function. These observations are different than other receptor systems, which require the induction of one or more of these pathways. Together, these data have defined more fully the mechanism for the TCR-induced phosphorylation of specific sites on Pyk2, suggesting that the TCR has a distinct pathway for the activation of Pyk2 compared with other receptor systems.

Key Words: TCR • signal transduction • kinases • biochemistry