© The Rockefeller University Press, 0022-1007/1997/4/1387/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 7, April 7, 1997 1387-1392
Role of Tyrosine Phosphorylation of HS1 in B Cell Antigen Receptor-mediated Apoptosis
Yuji Yamanashi*,
Takahiro Fukuda
,
Hirofumi Nishizumi*,
Tetsuya Inazu
,
Ken-ichi Higashi*,
Daisuke Kitamura||,
Takaomi Ishida*,
Hirohei Yamamura¶,
Takeshi Watanabe
, and
Tadashi Yamamoto*
From the * Department of Oncology, Institute of Medical Science, University of Tokyo, Tokyo 108, Japan;
Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-62, Japan;
Department of Biochemistry, Fukui Medical School, Fukui 910-11, Japan; || Research Institute for Bioscience, Science University of Tokyo, Noda 278, Japan; and the ¶ Department of Biochemistry, Kobe University, School of Medicine, Kobe 650, Japan
The 75-kD HS1 protein is highly tyrosine-phosphorylated during B cell antigen receptor (BCR)-mediated signaling. Owing to low expression of HS1, WEHI-231-derived M1 cells, unlike the parental cells, are insensitive to BCR-mediated apoptosis. Here, we show that BCR-associated tyrosine kinases Lyn and Syk synergistically phosphorylate HS1, and that Tyr378 and Tyr-397 of HS1 are the critical residues for its BCR-induced phosphorylation. In addition, unlike wild-type HS1, a mutant HS1 carrying the mutations Phe-378 and Phe-397 was unable to render M1 cells sensitive to apoptosis. Wild-type HS1, but not the mutant, localized to the nucleus under the synergy of Lyn and Syk. Thus, tyrosine phosphorylation of HS1 is required for BCR-induced apoptosis and nuclear translocation of HS1 may be a prerequisite for B cell apoptosis.
Address correspondence to Tadashi Yamamoto, Department of Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan. The current address for Y. Yamanashi is the Department of Biology, MIT, 77 Massachusetts Ave., Cambridge, MA 02139.

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