Differential activation of the ERK, JNK, and p38 mitogen-activated protein kinases by CD40 and the B cell antigen receptor.
Differential activation of the ERK, JNK, and p38 mitogen-activated protein kinases by CD40 and the B cell antigen receptor.
复制标题
CD40 和 B 细胞抗原受体对 ERK、JNK 和 p38 丝裂原激活蛋白激酶的差异激活。
DOI：
10.4049/jimmunol.157.8.3381
复制
发表时间：
1996
影响因子：
4.4
通讯作者：
M. Gold
中科院分区：
文献类型：
--
作者：
Claire L. Sutherland;A. Heath;S. Pelech;P. Young;M. Gold
参与CD40可阻止B细胞抗原受体（BCR）诱导的WEHI-231 B淋巴瘤细胞系的凋亡。我们利用该细胞系研究了丝裂原活化蛋白（MAP）激酶在整合BCR和CD40信号传导中的作用。三种类型的MAP激酶，细胞外信号调节激酶（ERKs）， c-Jun n末端激酶（JNKs）和p38，每一种都磷酸化一组不同的转录因子。因此，激活MAP激酶的不同组合可能导致不同的生物学反应。我们发现BCR在WEHI-231细胞中的作用导致ERK2的15- 20倍激活和ERK1的2- 3倍刺激。CD40不激活这两种激酶，也不影响bcr诱导的ERK激活。相比之下，CD40的参与导致JNK活动增加了50到70倍。BCR交联本身引起JNK活性适度（4- 8倍）增加，也增强了cd40诱导的JNK激活。最后，CD40引起p38激酶以及MAPKAP激酶-2 （p38的下游靶点）的强烈激活。BCR参与仅引起p38通路的弱激活。综上所述，BCR强激活ERK2，弱激活ERK1、JNK和p38，而CD40显著刺激JNK和p38激酶。因此，仅ERK2的激活与WEHI-231细胞的凋亡相关，而所有三种MAP激酶途径的完全激活与细胞存活相关。MAP激酶在调节这些反应中的作用仍有待检验。
B cell antigen receptor (BCR)-induced apoptosis in the WEHI-231 B lymphoma cell line can be prevented by engaging CD40. We have used this cell line to investigate the role of mitogen-activated protein (MAP) kinases in integrating BCR and CD40 signaling. Each of the three types of MAP kinases, the extracellular signal-regulated kinases (ERKs), the c-Jun N-terminal kinases (JNKs), and p38, phosphorylates a distinct set of transcription factors. Thus, activating different combinations of MAP kinases could lead to distinct biological responses. We found that BCR engagement in WEHI-231 cells caused a 15- to 20-fold activation of ERK2 and a 2- to 3-fold stimulation of ERK1. CD40 did not activate either of these kinases, nor did it affect BCR-induced ERK activation. In contrast, CD40 engagement caused a 50- to 70-fold increase in JNK activity. BCR cross-linking caused a modest (4- to 8-fold) increase in JNK activity by itself and also potentiated CD40-induced JNK activation. Finally, CD40 caused strong activation of the p38 kinase as well as MAPKAP kinase-2, a downstream target of p38. BCR engagement caused only weak activation of the p38 pathway. In summary, the BCR strongly activates ERK2 and weakly activates ERK1, JNK, and p38, while CD40 markedly stimulates the JNK and p38 kinases. Thus, activation of only ERK2 correlates with apoptosis in WEHI-231 cells, whereas full activation of all three MAP kinase pathways correlates with cell survival. The role of MAP kinases in regulating these responses remains to be tested.
DOI：
10.1073/pnas.89.14.6550
发表时间：
1992-07-15
影响因子：
11.1
作者：
NOELLE, RJ;ROY, M;ARUFFO, A
通讯作者：
ARUFFO, A