Ho H Y, Lee H H, Lai M Z
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Eur J Immunol. 1997 Jan;27(1):222-6. doi: 10.1002/eji.1830270133.
cAMP inhibits T cell activation by acting as an antagonist for selective kinases and transcriptional factors. We have recently demonstrated that cAMP inhibited c-Jun N-terminal kinase (JNK) but left the mitogen-activated protein (MAP) kinase cascade almost unaffected in T lymphocytes. In accordance with recent reports, we also observed a selective suppression of nuclear factor NF-kappaB activation by cAMP. The possible link between the JNK cascade and NF-kappaB activation was demonstrated by the fact that the active form of MAP kinase kinase kinase (deltaMEKK), a constitutive activator of JNK, induced NF-kappaB but not AP-1, Oct, and NF-AT in T cells. In contrast, the induction of MAP kinase kinase (MEK)-MAP kinase did not stimulate NF-kappaB activity. The specific activation of NF-kappaB by a single MEKK-JNK cascade was thus unusual, given that the activation of other transcriptional elements in T cells requires at least two signal pathways. This was further confirmed by the fact that cAMP inhibition of NF-kappaB activation was reversed by overexpression of deltaMEKK.
环磷酸腺苷（cAMP）通过作为选择性激酶和转录因子的拮抗剂来抑制T细胞活化。我们最近证明，cAMP抑制c-Jun氨基末端激酶（JNK），但在T淋巴细胞中丝裂原活化蛋白（MAP）激酶级联反应几乎不受影响。与最近的报道一致，我们还观察到cAMP对核因子NF-κB活化具有选择性抑制作用。JNK级联反应与NF-κB活化之间的可能联系通过以下事实得到证明：MAP激酶激酶激酶（deltaMEKK）的活性形式（JNK的组成型激活剂）在T细胞中诱导NF-κB，但不诱导AP-1、Oct和NF-AT。相反，MAP激酶激酶（MEK）-MAP激酶的诱导并未刺激NF-κB活性。鉴于T细胞中其他转录元件的活化至少需要两条信号通路，因此由单个MEKK-JNK级联反应对NF-κB进行特异性活化是不寻常的。deltaMEKK的过表达逆转了cAMP对NF-κB活化的抑制作用，这一事实进一步证实了上述观点。
