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

Kazumasa Yokoyama, I. Hsin Su, Tohru Tezuka, Tomoharu Yasuda, Katsuhiko Mikoshiba, Alexander Tarakhovsky, Tadashi Yamamoto

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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. Overexpression 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, BANKmediated calcium mobilization may be specific to foreign antigen-induced immune responses rather than to signaling required for B-cell development.

Original languageEnglish
Pages (from-to)83-92
Number of pages10
JournalEMBO Journal
Volume21
Issue number1-2
DOIs
Publication statusPublished - Jan 15 2002

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Yokoyama, K., Su, I. H., Tezuka, T., Yasuda, T., Mikoshiba, K., Tarakhovsky, A., & Yamamoto, T. (2002). BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP3 receptor. EMBO Journal, 21(1-2), 83-92. https://doi.org/10.1093/emboj/21.1.83