Chromatin-bound mitogen-activated protein kinases transmit dynamic signals in transcription complexes in β-cells
Chromatin-bound mitogen-activated protein kinases transmit dynamic signals in transcription complexes in β-cells
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DOI：
10.1073/pnas.0806465105
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发表时间：
2008-09-09
影响因子：
11.1
通讯作者：
Cobb, Melanie H.
中科院分区：
文献类型：
--
作者：
Lawrence, Michael C.;McGlynn, Kathleen;Cobb, Melanie H.
MAPK途径通过转录因子和其他DNA结合蛋白的磷酸化来调节转录。在胰腺β细胞中，ERK 1/2是胰岛素基因和其他几种基因对葡萄糖应答的转录所必需的。我们发现，葡萄糖敏感的转录激活因子和抑制因子的胰岛素基因启动子的结合依赖于ERK 1/2活性。我们还发现，葡萄糖和神经生长因子刺激ERK 1/2的胰岛素基因和其他启动子的结合。ERK 1/2级联模块，包括MEK 1/2和Rsk，被发现在与这些启动子结合的复合物中。这些发现意味着，MAPK信号复合物位于敏感的启动子与他们的蛋白质底物，以调节转录原位响应传入的信号。
MAPK pathways regulate transcription through phosphorylation of transcription factors and other DNA-binding proteins. In pancreatic beta-cells, ERK1/2 are required for transcription of the insulin gene and several other genes in response to glucose. We show that binding of glucose-sensitive transcription activators and repressors to the insulin gene promoter depends on ERK1/2 activity. We also find that glucose and NGF stimulate the binding of ERK1/2 to the insulin gene and other promoters. An ERK1/2 cascade module, including MEK1/2 and Rsk, are found in complexes bound to these promoters. These findings imply that MAPK-containing signaling complexes are positioned on sensitive promoters with their protein substrates to modulate transcription in situ in response to incoming signals.