Identification and mapping of protein kinase A binding sites in the costameric protein myospryn
Identification and mapping of protein kinase A binding sites in the costameric protein myospryn
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DOI：
10.1016/j.bbamcr.2007.04.004
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发表时间：
2007-06-01
影响因子：
5.1
通讯作者：
Naya, Francisco J.
中科院分区：
文献类型：
--
作者：
Reynolds, Joseph G.;McCalmon, Sarah A.;Naya, Francisco J.
最近，我们发现了MEF2A的一个新的靶基因，名为myospryn，它编码一种大的、肌肉特异性的、胞间限制性的α-肌动蛋白结合蛋白。Myospryn属于蛋白质中的三方基序(Trim)，是一种独立鉴定的结合障碍蛋白。Dybindin与α-dystrobrevin有关，α-dystrobrevin是肌肉中dystrophin糖蛋白复合体(DGC)的一种成分。除了这些最初的发现之外，关于myospryn在横纹肌中的潜在功能还知之甚少。在这里，我们揭示了myospryn是蛋白激酶A(PKA)(或AKAP)的锚定蛋白，其最接近的同源物是AKAP12，也称为Gravin/AKAP250/SSeCKS。我们证明了myospryn与PKA的II型调节亚基RIIα共同定位于横纹肌的外周Z盘/腔雄区。Myospryn与RIIα相互作用，这种支架功能在进化上是保守的，因为斑马鱼同源基因也与PKA相互作用。此外，myospryn是PKA的底物。这些发现表明，PKA信号定位于肌肉的肋骨。(C)2007 Elsevier B.V.保留所有权利。
Recently we identified a novel target gene of MEF2A named myospryn that encodes a large, muscle-specific, costamere-restricted alpha-actinin binding protein. Myospryn belongs to the tripartite motif (TRIM) superfarnily of proteins and was independently identified as a dysbindin-interacting protein. Dysbindin is associated with alpha-dystrobrevin, a component of the dystrophin-glycoprotein complex (DGC) in muscle. Apart from these initial findings little else is known regarding the potential function of myospryn in striated muscle. Here we reveal that myospryn is an anchoring protein for protein kinase A (PKA) (or AKAP) whose closest homolog is AKAP12, also known as gravin/AKAP250/SSeCKS. We demonstrate that myospryn co-localizes with RII alpha, a type II regulatory subunit of PKA, at the peripheral Z-disc/costameric region in striated muscle. Myospryn interacts with RII alpha and this scaffolding function has been evolutionarily conserved as the zebrafish ortholog also interacts with PKA. Moreover, myospryn serves as a substrate for PKA. These findings point to localized PKA signaling at the muscle costamere. (c) 2007 Elsevier B.V. All rights reserved.