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首页> 外文期刊>Cellular Signalling >Nuclear receptors: integration of multiple signalling pathways through phosphorylation [Review]
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Nuclear receptors: integration of multiple signalling pathways through phosphorylation [Review]

机译：核受体：通过磷酸化整合多种信号通路[综述]

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摘要

Nuclear receptors (NRs) orchestrate the transcription of specific gene networks in response to binding of their cognate ligand. They also act as mediators in a variety of signalling pathways through integrating diverse phosphorylation events. NR phosphorylation concerns all three major domains, the N-terminal activation function (AF-1), the ligand-binding and the DNA binding domains. Often, phosphorylation of NRs by kinases that are associated with general transcription factors (e.g. cdk7 within TFIIH), or activated in response to a variety of signals (MAPKs, Akt, PKA, PKC), facilitates the recruitment of coactivators or of components of the transcription machinery and, therefore, cooperates with the ligand to enhance transcription activation. But phosphorylation can also contribute to the termination of the ligand response through inducing DNA dissociation or NR degradation or through decreasing ligand affinity. These different modes of regulation reveal an unexpected complexity of the dynamics of NR-mediated transcription. In addition, deregulation of NR phosphorylation may impact their action in certain diseases or cancers. (C) 2002 Elsevier Science Inc. All rights reserved. [References: 137]
机译：核受体（NRs）响应其同源配体的结合，协调特定基因网络的转录。它们还通过整合各种磷酸化事件而在多种信号传导途径中充当介体。 NR磷酸化涉及所有三个主要域，N末端激活功能（AF-1），配体结合和DNA结合域。通常，NRs被与一般转录因子（例如TFIIH中的cdk7）相关联的激酶磷酸化，或响应多种信号（MAPK，Akt，PKA，PKC）而被激活，从而促进了共激活因子或其组成部分的募集。转录机制，并因此与配体配合以增强转录激活。但是，磷酸化也可以通过诱导DNA解离或NR降解或通过降低配体亲和力来终止配体响应。这些不同的调节模式揭示了NR介导的转录动力学的意外复杂性。此外，NR磷酸化的失调可能会影响其在某些疾病或癌症中的作用。 （C）2002 Elsevier Science Inc.保留所有权利。 [参考：137]

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