Immunology The BCR BANKs on the IP₃ Receptor

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-2 (PLC-2) activity, which is known to mediate the release of Ca²⁺ from intracellular stores. These data suggest that BANK activated Ca²⁺ mobilization independent of PLC-2. 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-2 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]