| pubmed-article:8871635 | pubmed:abstractText | 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. | lld:pubmed |
