A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells.
Chat (Cas/HEF1-associated signal transducer) is a novel adaptor protein with an N-terminal Src homology-2 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 production after costimulation of T cell receptor and CD28. The degree of JNK activation is enhanced substantially in the Chat-H transfectants upon costimulation. The Src homology-2 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 interleukin-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 costimulatory signals.
Sakakibara
Akira
A
Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.
Hattori
Seisuke
S
Nakamura
Shun
S
Katagiri
Takuya
T
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D018106:CD28 Antigens / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D006410:Hematopoiesis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; D002352:Carrier Proteins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; C405695:Sh2d3c protein, mouse; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases