Editors' ChoiceImmunology

The BCR BANKs on the IP3 Receptor

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Science's STKE  15 Jan 2002:
Vol. 2002, Issue 115, pp. tw22
DOI: 10.1126/stke.2002.115.tw22

Yokoyama et al. have cloned and characterized a new protein involved in B cell receptor (BCR)-mediated Ca2+ mobilization. The B cell scaffold protein with ankyrin repeats (mercifully termed BANK) functioned as a docking protein that functionally coupled the BCR to inositol trisphosphate receptor (IP3R) activation. BCR activation led to the tyrosine phosphorylation of BANK. Cells that overexpressed BANK had increased IP3R-dependent Ca2+ mobilization, but did not contain increased phospholipase C-γ2 (PLC-γ2) activity, which is known to mediate the release of Ca2+ from intracellular stores. These data suggest that BANK activated Ca2+ mobilization independent of PLC-γ2. BANK existed in a tripartite protein complex with the protein tyrosine kinase Lyn and IP3R in vivo. Genetic mapping indicated that IP3R bound to a region of BANK consisting of amino acids 1 to 154, whereas Lyn interacted with BANK between amino acids 367 and 653. BANK mRNA was expressed in BCR-containing B cells, but not in early, immature B cells, suggesting that BANK does not participate in B cell development, but may be important for BCR-mediated signaling. Thus, the BCR can activate Ca2+ mobilization independently of the well studied PLC-γ2 pathway; however, further studies will be needed to identify why a second pathway is needed.

K. Yokoyama, I.-h. Su, T. Tezuka, T. Yasuda, K. Mikoshiba, A. Tarakhovsky, T. Yamamoto, BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP3 receptor. EMBO J. 21, 83-92 (2002). [Abstract] [Full Text]

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