通过锚定到mAKAPα对PDK1激活级联进行空间限制。
Spatial restriction of PDK1 activation cascades by anchoring to mAKAPalpha.
作者信息
Michel Jennifer J Carlisle, Townley Ian K, Dodge-Kafka Kimberly L, Zhang Fang, Kapiloff Michael S, Scott John D
机构信息
Howard Hughes Medical Institute and Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.
出版信息
Mol Cell. 2005 Dec 9;20(5):661-72. doi: 10.1016/j.molcel.2005.10.013.
The muscle A-kinase anchoring protein (mAKAP) tethers cAMP-dependent enzymes to perinuclear membranes of cardiomyocytes. We now demonstrate that two alternatively spliced forms of mAKAP are expressed: mAKAPalpha and mAKAPbeta. The longer form, mAKAPalpha, is preferentially expressed in the brain. mAKAPbeta 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 mAKAPalpha 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 mAKAPalpha 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.
肌肉A激酶锚定蛋白（mAKAP）将环磷酸腺苷（cAMP）依赖性酶系于心肌细胞的核周膜上。我们现在证明，mAKAP存在两种可变剪接形式：mAKAPα和mAKAPβ。较长的形式mAKAPα优先在脑中表达。mAKAPβ是锚定蛋白的较短形式，缺少前244个氨基酸，优先在心脏中表达。mAKAPα独特的氨基末端可在空间上限制3-磷酸肌醇依赖性激酶-1（PDK1）的活性。生化和遗传学分析表明，将PDK1和细胞外信号调节激酶（ERK）同时招募到mAKAPα上有助于下游靶点p90核糖体S6激酶（p90RSK）的激活和释放。组织特异性信号复合物的组装提供了一种有效的机制，可将脂质介导的信号和有丝分裂激活信号整合并传递至细胞核。
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