TY - JOUR
T1 - BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP3 receptor
AU - Yokoyama, Kazumasa
AU - Su, I. Hsin
AU - Tezuka, Tohru
AU - Yasuda, Tomoharu
AU - Mikoshiba, Katsuhiko
AU - Tarakhovsky, Alexander
AU - Yamamoto, Tadashi
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002/1/15
Y1 - 2002/1/15
N2 - 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.
AB - 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.
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U2 - 10.1093/emboj/21.1.83
DO - 10.1093/emboj/21.1.83
M3 - Article
C2 - 11782428
AN - SCOPUS:0037080952
VL - 21
SP - 83
EP - 92
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 1-2
ER -