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Bruton’s Tyrosine Kinase (Btk) in Mast Cell Activation

Dr. Kawakami has been using the high-affinity IgE receptor (FceRI) signaling in mast cells as a model system. Following his co-discovery of two Tec family PTKs, Btk and Itk, in mast cells, his group revealed crucial roles of these kinases in FceRI-mediated activation and apoptosis. By introducing retroviral transduction into the field of mast cell research, they established a standard methodology to investigate the FceRI signaling system.

Selected References
Yamada, N., Kawakami, Y., Kimura, H., Fukamachi, H., Baier, G., Altman, A., Kato, T., Inagaki, Y., and Kawakami, T. Structure and expression of novel protein-tyrosine kinases, Emb and Emt, in hematopoietic cells. Biochem. Biophys. Res. Comm. 192:231-240, 1993.

Kawakami, Y., Yao, L., Miura, T., Tsukada, S., Witte, O. N., and Kawakami, T. Tyrosine
phosphorylation and activation of Bruton tyrosine kinase (Btk) upon FceRI cross-linking. Mol. Cell. Biol. 14:5108-5113, 1994.

Kawakami, Y., Miura, T., Bissonnette, R., Hata, D., Khan, W. N., Kitamura, T., Maeda-Yamamoto, M., Hartman, S. E., Yao, L., Alt, F. W., and Kawakami, T. Bruton’s tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity. Proc. Natl. Acad. Sci. USA 94:3938-3942, 1997.

Hata, D., Kawakami, Y., Inagaki, N., Lantz, C. S., Kitamura, T., Khan, W. N., Tashiro, M., Maeda-
Yamamoto, M., Miura, T., Han, W., Hartman, S. E., Yao, L., Nagai, H., Goldfeld, A. E., Alt, F. W., Galli, S. J., Witte, O. N., and Kawakami, T. Involvement of Bruton’s tyrosine kinase in FceRI-dependent mast cell degranulation and cytokine production. J. Exp. Med. 187:1235-1247, 1998.