BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP(3) receptor.
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 (IP(3)R) associate with the distinct regions of BANK and that BANK promotes Lyn-mediated tyrosine phosphorylation of IP(3)R. Given that IP(3)R 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 IP(3)R. 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.
Yokoyama
Kazumasa
K
Department of Oncology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Su Ih
I-hsin
IH
Tezuka
Tohru
T
Yasuda
Tomoharu
T
Mikoshiba
Katsuhiko
K
Tarakhovsky
Alexander
A
Yamamoto
Tadashi
T
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017089:Ankyrin Repeat; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C447641:BANK1 protein, human; D015220:Calcium Channels; D002352:Carrier Proteins; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D014443:Tyrosine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases