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21 (1): 83-92

Copyright © 2002 by the European Molecular Biology Organization.

BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP3 receptor

Kazumasa Yokoyama, I-hsin Su1, Tohru Tezuka, Tomoharu Yasuda2, Katsuhiko Mikoshiba3, Alexander Tarakhovsky1, and Tadashi Yamamoto4

Department of Oncology and 3Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan and 1Laboratory of Lymphocyte Signaling, the Rockefeller University, New York, NY 10021, USA 2Present address: Department of Tumor Virology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan 4Corresponding author e-mail: tyamamot{at}ims.u-tokyo.ac.jp

Abstract: B-cell activation mediated through the antigen receptor is dependent on activation of protein tyrosine kinases (PTKs) such as Lyn and Syk and subsequent phosphorylation of various signaling proteins. Here we report on the identification and characterization of the B-cell scaffold protein with ankyrin repeats (BANK), a novel substrate of tyrosine kinases. BANK is expressed in B cells and is tyrosine phosphorylated upon B-cell antigen receptor (BCR) stimulation, which is mediated predominantly by Syk. Overexpres sion of BANK in B cells leads to enhancement of BCR-induced calcium mobilization. We found that both Lyn and inositol 1,4,5-trisphosphate receptor (IP3R) associate with the distinct regions of BANK and that BANK promotes Lyn-mediated tyrosine phosphorylation of IP3R. Given that IP3R channel activity is up-regulated by its tyrosine phosphorylation, BANK appears to be a novel scaffold protein regulating BCR-induced calcium mobilization by connecting PTKs to IP3R. Because BANK expression is confined to functional BCR-expressing B cells, BANK-mediated calcium mobilization may be specific to foreign antigen-induced immune responses rather than to signaling required for B-cell development.

Key Words: Keywords: B-cell antigen receptor/calcium mobilization/inositol 1,4,5-trisphosphate receptor/scaffold protein/tyrosine phosphorylation

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