Cooperation between Syk and Rac1 leads to synergistic JNK activation in T lymphocytes
Cooperation between Syk and Rac1 leads to synergistic JNK activation in T lymphocytes
复制标题
DOI：
10.1016/s1074-7613(00)80456-2
复制
发表时间：
1998-01-01
期刊：
影响因子：
32.4
通讯作者：
Karin, M
中科院分区：
文献类型：
--
作者：
Jacinto, E;Werlen, G;Karin, M
在T细胞的共刺激过程中，MAP激酶（MAPK）JNK而不是ERK被协同激活。我们研究了蛋白酪氨酸激酶（PTKs）和GTP酶如何差异调节T细胞中的JNK和ERK。虽然PTK不是选择性的，但小GTP酶显示不同的MAPK激活功能。Ras激活ERK，Rac激活JNK。Rac与Syk产生的信号合作以增强JNK活化，并且似乎处于从CD 28、钙调神经磷酸酶和蛋白激酶C发出的途径的节点。AP-1和NF-AT依赖性报告基因受Rac和Syk刺激，并依赖于JNK。与Syk不同，PTK Lck激活JNK，但不与Pac合作，导致AP-1和NF-AT激活较弱。因此，由PTK产生的信号在功能上是不同的，需要整合以诱导转录反应。
The MAP kinase (MAPK) JNK but not ERK is synergistically activated during costimulation of T cells. We examined how protein tyrosine kinases (PTKs) and GTPases differentially regulate JNK and ERK in T cells. While PTKs are not selective, small GTPases display distinct MAPK-activating functions. Whereas Ras activates ERK, Rac activates JNK. Rac cooperates with a Syk-generated signal to enhance JNK activation and appears to be at a nodal point for pathways emanating from CD28, calcineurin, and protein kinase C. AP-1-and NF-AT-dependent reporters are stimulated by Rac and Syk and are dependent on JNK. Unlike Syk, the PTK Lck activates JNK but does not cooperate with Pac, resulting in weak AP-1 and NF-AT activation. Therefore, signals generated by PTKs are functionally distinct and need to be integrated to induce transcriptional responses.