The p38 mitogen-activated protein kinase is activated by ligation of the T or B lymphocyte antigen receptors, Fas or CD40, but suppression of kinase activity does not inhibit apoptosis induced by antigen receptors.
The p38 mitogen-activated protein kinase is activated by ligation of the T or B lymphocyte antigen receptors, Fas or CD40, but suppression of kinase activity does not inhibit apoptosis induced by antigen receptors.
复制标题
p38 丝裂原激活蛋白激酶通过连接 T 或 B 淋巴细胞抗原受体、Fas 或 CD40 来激活，但抑制激酶活性并不能抑制抗原受体诱导的细胞凋亡。
DOI：
10.4049/jimmunol.159.11.5309
复制
发表时间：
1997
影响因子：
4.4
通讯作者：
John W. Schrader
中科院分区：
文献类型：
--
作者：
R. A. Salmon;Ian Foltz;P. Young;John W. Schrader
我们研究了正常小鼠T和B细胞中p38丝裂原活化蛋白激酶（MAPK）的活化及其在凋亡中的作用。增殖T细胞上TCR复合物的CD 3链的交联导致p38 MAPK和MAPKAP激酶-2的活化。CD 28的交联不能激活p38 MAPK或MAPKAP激酶-2，但与低剂量的抗CD 3有强烈的协同作用。T细胞上Fas的交联也诱导p38 MAPK和MAPKAP激酶-2的快速活化。使用特异性抑制剂SB 203580，MAPKAP激酶-2响应于CD 3、Fas或CD 3和CD 28的交联的体内活化显示依赖于p38 MAPK活性。当SB 203580以抑制体内MAPKAP激酶-2活化的浓度使用时，SB 203580不抑制T细胞中活化诱导的细胞死亡。B细胞Ag受体（BCR）或CD 40在新鲜分离的或LPS活化的脾B细胞或未成熟B淋巴瘤WEHI 231上的交联导致p38 MAPK和MAPKAP激酶-2的活化。SB 203580在WEHI 231细胞中抑制p38 MAPK活性对BCR诱导的凋亡或抗CD 40介导的凋亡抑制均无影响。我们的结论是，激活p38 MAPK和MAPKAP激酶-2交联的TCR，BCR，Fas，或CD 40是不相关的作用，在调节淋巴细胞存活，抑制激酶活性并不抑制诱导细胞凋亡。
We have investigated the activation of the p38 mitogen-activated protein kinase (MAPK) in normal mouse T and B cells and its role in apoptosis. Cross-linking of the CD3 chains of the TCR complex on proliferating T cells resulted in activation of p38 MAPK and MAPKAP kinase-2. Cross-linking of CD28 failed to activate p38 MAPK or MAPKAP kinase-2, but synergized strongly with low doses of anti-CD3. Cross-linking of Fas on T cells also induced rapid activation of p38 MAPK and MAPKAP kinase-2. The in vivo activation of MAPKAP kinase-2 in response to cross-linking of CD3, Fas, or CD3 and CD28 was shown to be dependent on p38 MAPK activity using a specific inhibitor, SB 203580. SB 203580 did not inhibit activation-induced cell death in T cells when used at concentrations that suppressed activation of MAPKAP kinase-2 in vivo. Cross-linking of the B cell Ag receptor (BCR) or CD40 on freshly isolated or LPS-activated splenic B cells or the immature B lymphoma, WEHI 231, resulted in activation of p38 MAPK and MAPKAP kinase-2. In vivo inhibition of p38 MAPK activity in WEHI 231 cells by SB 203580 had no effect on either BCR-induced apoptosis or anti-CD40-mediated suppression of apoptosis. We conclude that the activation of p38 MAPK and MAPKAP kinase-2 by cross-linking of the TCR, BCR, Fas, or CD40 was not correlated with their roles in regulating lymphocyte survival, and that suppression of kinase activity did not inhibit the induction of apoptosis.