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Papers In Press, published online ahead of print December 14, 2002
J. Biol. Chem, 10.1074/jbc.M207942200
Submitted on August 5, 2002
Revised on December 14, 2002
Accepted on December 14, 2002

A novel hematopoietic adaptor protein, Chat-H, positively regulates T-cell receptor-mediated interleukin-2 production by Jurkat cells

Akira Sakakibara, Seisuke Hattori, Shun Nakamura, and Takuya Katagiri

Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639

Corresponding Author: katagiri{at}ims.u-tokyo.ac.jp

Chat (Cas/HEF1-associated signal transducer) is a novel adaptor protein with an N-terminal SH2 domain and C-terminal Cas/HEF1 association domain. We report here the molecular cloning of Chat-H, the hematopoietic isoform of Chat. Chat-H has an extended N-terminal domain besides the known Chat domain structures, suggesting a unique function of Chat-H in hematopoietic cells. Jurkat transfectants overexpressing Chat-H show a marked increase in interleukin-2 (IL-2) production following co-stimulation of T-cell receptor and CD28. The degree of JNK activation is substantially enhanced in the Chat-H transfectants upon co-stimulation. The SH2 domain mutant of Chat-H loses this signal modulating activity. Expression of the Cas/HEF1 association domain mutant exhibits a dominant negative effect on both JNK activation and IL-2 production. We further found that Chat-H forms a complex with Pyk2H and enhances its tyrosine-402-phosphorylation, an up-regulator of the JNK pathway. These results suggest that Chat-H positively controls T-cell function via integrating the co-stimulatory signals.


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