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.
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Grossmann, M
;
O'Reilly, LA
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
O'Reilly, LA
;
Gugasyan, R
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Gugasyan, R
;
Strasser, A
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Strasser, A
;
Adams, JM
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Adams, JM
;
Gerondakis, S
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Grossmann, M
;
O'Reilly, LA
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
O'Reilly, LA
;
Gugasyan, R
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Gugasyan, R
;
Strasser, A
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Strasser, A
;
Adams, JM
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
Adams, JM
;
Gerondakis, S
论文数: 0引用数: 0
h-index: 0
机构:
Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, AustraliaRoyal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia