Li Y Y, Baccam M, Waters S B, Pessin J E, Bishop G A, Koretzky G A
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242, USA.
J Immunol. 1996 Aug 15;157(4):1440-7.
CD40 is a 45- to 50-kDa transmembrane glycoprotein that plays an important role in B cell proliferation, survival, memory, and Ig isotype switching. How CD40 engagement couples to these distal events in B cell activation remains poorly understood. In this study, we have examined signal transduction events mediated by CD40 cross-linking in resting murine splenic B cells. In comparison to signaling via the B cell Ag receptor (BCR), CD40 cross-linking was less effective at activating protein tyrosine kinases. Interestingly, however, CD40 engagement resulted in the phosphorylation of both extracellular signal-regulated protein kinase (ERK) and the Ras guanine nucleotide exchange factor, Son of sevenless. In addition, both ERK and c-Jun NH2-terminal kinase activities were increased after both CD40 and BCR ligation. Overnight treatment of cells with phorbol ester as well as pharmacologic inhibitors of protein kinase C abrogated these signaling events after BCR treatment; however, no effect was seen on CD40-mediated activation of ERK or c-Jun NH2-terminal kinase, suggesting that the BCR and CD40 differentially utilize protein kinase C to couple with these signaling pathways.
CD40是一种45至50千道尔顿的跨膜糖蛋白，在B细胞增殖、存活、记忆及Ig同种型转换中发挥重要作用。CD40的激活如何与B细胞活化中的这些远端事件相偶联仍知之甚少。在本研究中，我们检测了静息小鼠脾脏B细胞中由CD40交联介导的信号转导事件。与通过B细胞抗原受体（BCR）进行的信号传导相比，CD40交联在激活蛋白酪氨酸激酶方面效果较差。然而，有趣的是，CD40的激活导致细胞外信号调节蛋白激酶（ERK）和Ras鸟嘌呤核苷酸交换因子（七号less之子，Son of sevenless）发生磷酸化。此外，在CD40和BCR连接后，ERK和c-Jun NH2末端激酶的活性均增加。用佛波酯以及蛋白激酶C的药理抑制剂对细胞进行过夜处理，消除了BCR处理后的这些信号事件；然而，对CD40介导的ERK或c-Jun NH2末端激酶的激活没有影响，这表明BCR和CD40在与这些信号通路偶联时对蛋白激酶C的利用存在差异。
