The p38 mitogen-activated protein kinase pathway in activated and anergic Th1 cells
The p38 mitogen-activated protein kinase pathway in activated and anergic Th1 cells
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DOI：
10.1006/cimm.1997.1182
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发表时间：
1997-09-15
影响因子：
4.3
通讯作者：
Scherle, PA
中科院分区：
文献类型：
--
作者：
DeSilva, DR;Jones, EA;Scherle, PA
通过TCR刺激T细胞可激活丝裂原活化蛋白激酶(MAPK)家族成员ERK(细胞外信号调节激酶)和JNK(Jun NH2末端激酶)。这些激酶协同作用，增加转录因子AP-1的活性，而AP-1参与IL-2的转录上调。最近，第三个MAPK成员p38已经被发现。T细胞激活对这一途径的影响尚未阐明。使用两个小鼠Th1克隆，我们证明了p38通路是在抗CD3+抗CD28交联剂或PMA+离子霉素刺激下诱导的。P38活性可被抗CD3或PMA单独诱导，即使在低水平的TCR信号下，共刺激也不能增强p38的活性。P38活性在20min时达到高峰，2小时后显著下降。无能(耐受)Th1细胞表现出p38活性降低以及ERK和JNK活性降低，即使这些蛋白的水平保持不变。(C)1997年学术出版社。
Stimulation of T cells through the TCR leads to activation of the mitogen-activated protein kinase (MAPK) family members ERK (extracellular signal-regulated kinase) and JNK (jun NH2-terminal kinase). These kinases act in synergy to increase the activity of the transcription factor AP-1 which is involved in the transcriptional upregulation of IL-2. Recently a third MAPK member, p38, has been identified. The effects of T cell activation on this pathway have not yet been elucidated. Using two murine Th1 clones, we demonstrate that the p38 pathway is induced upon anti-CD3 plus anti-CD28 crosslinking or PMA plus ionomycin stimulation. p38 activity was induced fully by anti-CD3 or PMA alone and is not enhanced by costimulation even at low levels of TCR signaling. p38 activity peaked at 20 min and was significantly decreased by 2 hr. Anergic (tolerant) Th1 cells showed decreased p38 activity as well as decreased ERK and JNK activities even though levels of these proteins remained unchanged. (C) 1997 Academic Press.