The B lymphocyte adaptor molecule of 32 kD (Bam32) regulates B cell antigen receptor signaling and cell survival

被引:51
作者
Niiro, H
Maeda, A
Kurosaki, T
Clark, EA
机构
[1] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA
[2] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
[3] Kansai Med Univ, Inst Liver Res, Dept Mol Genet, Moriguchi, Osaka 5708506, Japan
关键词
adaptor protein; cell death; germinal center; PH domain; signal transduction;
D O I
10.1084/jem.20011524
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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)gamma2, 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)gamma2. 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 K binding (NF-kappaB) 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.
引用
收藏
页码:143 / 149
页数:7
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