Spatial restriction of PDK1 activation cascades by anchoring to mAKAPα
Spatial restriction of PDK1 activation cascades by anchoring to mAKAPα
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DOI：
10.1016/j.molcel.2005.10.013
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发表时间：
2005-12-09
期刊：
影响因子：
16
通讯作者：
Scott, JD
中科院分区：
文献类型：
--
作者：
Michel, JJC;Townley, IK;Scott, JD
肌肉A激酶锚定蛋白（mAKAP）将cAMP依赖性酶系到心肌细胞的核周膜。我们现在证明了mAKAP的两种选择性剪接形式表达：mAKAP α和mAKAP β。较长的形式，mAKAP α，优先在大脑中表达。mAKAP β是锚定蛋白的较短形式，缺少前244个氨基酸，并且优先在心脏中表达。mAKAP α独特的氨基末端可以在空间上限制3-磷酸肌醇依赖性激酶-1（PDK 1）的活性。生物化学和遗传分析表明，PDK 1和ERK同时募集到mAKAP α上促进下游靶点p90 RSK的激活和释放。组织特异性信号复合物的组装提供了将脂质介导的和促有丝分裂激活的信号整合和中继到细胞核的有效机制。
The muscle A-kinase anchoring protein (mAKAP) tethers cAMP-dependent enzymes to perinuclear membranes of cardiornyocytes. We now demonstrate that two alternatively spliced forms of mAKAP are expressed: mAKAP alpha and mAKAP beta. The longer form, mAKAP alpha, is preferentially expressed in the brain. mAKAP beta is a shorter form of the anchoring protein that lacks the first 244 amino acids and is preferentially expressed in the heart. The unique amino terminus of mAKAP alpha can spatially restrict the activity of 3-phosphoinositide-dependent kinase-1 (PDK1). Biochemical and genetic analyses demonstrate that simultaneous recruitment of PDK1 and ERK onto mAKAP alpha facilitates activation and release of the downstream target p90RSK. The assembly of tissue-specific signaling complexes provides an efficient mechanism to integrate and relay lipid-mediated and mitogenic activated signals to the nucleus.