scholarly journals The B Lymphocyte Adaptor Molecule of 32 kD (Bam32) Regulates B Cell Antigen Receptor Signaling and Cell Survival

2002 ◽  
Vol 195 (1) ◽  
pp. 143-149 ◽  
Author(s):  
Hiroaki Niiro ◽  
Akito Maeda ◽  
Tomohiro Kurosaki ◽  
Edward A. Clark
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
Phospholipase C ◽  
B Lymphocyte ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Nuclear Factor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

The B lymphocyte–associated adaptor protein 32 kD in size (Bam32) is expressed at high levels in germinal center (GC) B cells. It has an NH2-terminal src homology 2 (SH2) domain which binds phospholipase C (PLC)γ2, and a COOH-terminal pleckstrin homology (PH) domain. Thus, Bam32 may function to integrate protein tyrosine kinase (PTK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways in B cells. To further define the role Bam32 plays in B cells, we generated Bam32-deficient DT40 cells. These Bam32−/− cells exhibited lower levels of B cell antigen receptor (BCR)-induced calcium mobilization with modest decreases in tyrosine phosphorylation of phospholipase C (PLC)γ2. Moreover, BCR-induced activation of extracellular signal-regulated kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) pathways was impaired in Bam32−/− cells but not the activation of Akt-related pathways. Activation of downstream transcription factors such as nuclear factor of activated T cells (NF-AT) and nuclear factor of κ binding (NF-κB) was also impaired in Bam32−/− cells. Furthermore, Bam32−/− cells were more susceptible to BCR-induced death. Taken together, these findings suggest that Bam32 functions to regulate BCR-induced signaling and cell survival most likely in germinal centers.

scholarly journals A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2.

1996 ◽  
Vol 184 (1) ◽  
pp. 31-40 ◽  
Author(s):  
M Takata ◽  
T Kurosaki
Keyword(s):  
B Cells ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Phospholipase C ◽  
Antigen Receptor ◽  
Bruton’S Tyrosine Kinase ◽  
B Cell Antigen Receptor ◽  
Bruton's Tyrosine Kinase ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-gamma 2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCR-coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-gamma 2 activation. Since Syk is also required for the BCR-induced PLC-gamma 2 activation, our findings indicate that PLC-gamma 2 activation is regulated by Btk and Syk through their concerted actions.

Identification of the SH2 Domain Binding Protein of Bruton’s Tyrosine Kinase as BLNK—Functional Significance of Btk-SH2 Domain in B-Cell Antigen Receptor-Coupled Calcium Signaling

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2357-2364 ◽  
Author(s):  
Shoji Hashimoto ◽  
Akihiro Iwamatsu ◽  
Masamichi Ishiai ◽  
Katsuya Okawa ◽  
Tomoki Yamadori ◽  
...  
Keyword(s):  
B Cells ◽  
Tyrosine Kinase ◽  
Calcium Signaling ◽  
B Cell ◽  
Functional Significance ◽  
Antigen Receptor ◽  
Sh2 Domain ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Bruton’s tyrosine kinase (Btk) is a critical component in the B-cell antigen receptor (BCR)-coupled signaling pathway. Its deficiency in B cells leads to loss or marked reduction in the BCR-induced calcium signaling. It is known that this BCR-induced calcium signaling depends on the activation of phospholipase Cγ (PLCγ), which is mediated by Btk and another tyrosine kinase Syk and that the SH2 and pleckstrin homology (PH) domains of Btk play important roles in this activation process. Although the importance of the PH domain of Btk has been explained by its role in the membrane targeting of Btk, the functional significance of the SH2 domain in the calcium signaling has remained merely a matter of speculation. In this report, we identify that one of the major Btk-SH2 domain-binding proteins in B cells is BLNK (B-cell linker protein) and present evidences that the interaction of BLNK and the SH2 domain of Btk contributes to the complete tyrosine phosphorylation of PLCγ.

B-cell antigen receptor activates transcription factors NFAT (nuclear factor of activated T-cells) and NF-κB (nuclear factor κB) via a mechanism that involves diacylglycerol

2004 ◽  
Vol 32 (1) ◽  
pp. 113-115 ◽  
Author(s):  
P. Antony ◽  
J.B. Petro ◽  
G. Carlesso ◽  
N.P. Shinners ◽  
J. Lowe ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
B Cell ◽  
Antigen Receptor ◽  
Nuclear Factor Κb ◽  
B Cell Antigen Receptor ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Engagement of the B-cell antigen receptor (BCR) induces the activation of various transcription factors, including NFAT (nuclear factor of activated T-cells) and NF-κB (nuclear factor κB), which participate in long-term biological responses such as proliferation, survival and differentiation of B-lymphocytes. We addressed the biochemical basis of this process using the DT40 chicken B-cell lymphoma. We discovered that Bruton's tyrosine kinase (BTK) and phospholipase C-γ2 (PLC-γ2) are required to activate NFAT and NF-κB, and to produce the lipid second messenger diacylglycerol in response to BCR cross-linking. Therefore the functional integrity of the BTK/PLC-γ2/diacylglycerol signalling axis is crucial for BCR-directed activation of both transcription factors NFAT and NF-κB.

scholarly journals Grb2 and GRAP connect the B cell antigen receptor to Erk MAP kinase activation in human B cells

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Kanika Vanshylla ◽  
Caren Bartsch ◽  
Christoffer Hitzing ◽  
Laura Krümpelmann ◽  
Jürgen Wienands ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Map Kinase ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Kinase Activation ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Human B Cells
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