Primary structure and function of an A kinase anchoring protein associated with calcium channels
Primary structure and function of an A kinase anchoring protein associated with calcium channels
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DOI：
10.1016/s0896-6273(00)80482-1
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发表时间：
1998-05-01
期刊：
影响因子：
16.2
通讯作者：
Murphy, BJ
中科院分区：
文献类型：
--
作者：
Gray, PC;Johnson, BD;Murphy, BJ
骨骼肌L型钙通道的快速、电压依赖性增强需要cAMP依赖的蛋白激酶的磷酸化，该蛋白激酶通过A激酶锚定蛋白锚定。本文报道了AKAP15的分离、初步序列测定和功能鉴定。AKAP15是一种含有81个氨基酸残基的脂质锚定蛋白，带有一个两亲性螺旋，与PKA结合，与横管中的L型钙通道共定位，并与转基因细胞中的L型钙通道相关。AKAP15的一个包含RII结合域的多肽片段阻断了电压依赖的增强作用。这些结果表明，AKAP15靶向于钙通道上的PKA，在电压依赖性增强和调节骨骼肌收缩中起关键作用。AKAP15在脑和心脏中的表达提示，它可能介导了PKA对神经元和心肌细胞中L类钙通道的快速调节。
Rapid, voltage-dependent potentiation of skeletal muscle L-type calcium channels requires phosphorylation by cAMP-dependent protein kinase (PKA) anchored via an A kinase anchoring protein (AKAP). Here we report the isolation, primary sequence determination, and functional characterization of AKAP15 a lipid-anchored protein of 81 amino acid residues with a single amphipathic helix that binds PKA, AKAP15 co-localizes with L-type calcium channels in transverse tubules and is associated with L-type calcium channels in transfected cells. A peptide fragment of AKAP15 encompassing the RII-binding domain blocks voltage-dependent potentiation. These results indicate that AKAP15 targets PKA to the calcium channel and plays a critical role in voltage-dependent potentiation and regulation of skeletal muscle contraction. The expression of AKAP15 in the brain and heart suggests that it may mediate rapid PKA regulation of L-type calcium channels in neurons and cardiac myocytes.