AMY-1 interacts with S-AKAP84 and AKAP95 in the cytoplasm and the nucleus, respectively, and inhibits cAMP-dependent protein kinase activity by preventing binding of its catalytic subunit to A-kinase-anchoring protein (AKAP) complex
AMY-1 interacts with S-AKAP84 and AKAP95 in the cytoplasm and the nucleus, respectively, and inhibits cAMP-dependent protein kinase activity by preventing binding of its catalytic subunit to A-kinase-anchoring protein (AKAP) complex
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DOI：
10.1074/jbc.m206387200
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发表时间：
2002-12-27
影响因子：
4.8
通讯作者：
Ariga, H
中科院分区：
文献类型：
--
作者：
Furusawa, M;Taira, T;Ariga, H
我们已经报道了一种新的c-Myc结合蛋白AMY-1与cAMP依赖性蛋白激酶锚定蛋白149（AKAP 149）及其剪接变体AKAP 84结合，并以与cAMP依赖性蛋白激酶（PKA）的调节亚基RII的复合物定位于线粒体中（Furusawa，M.，Ohnishi，T.，Taira，T.，Iguchi-Ariga，S. M. M.，和Axiga，H.（2001）J.Biol.Chem.276，36647-36651）。在这项研究中，我们进一步发现，AMY-1竞争性结合无论是AKAP 95或AKAP 84在细胞核和细胞质中，分别在浓度依赖性的方式，无论是AKAP。与AKAP 84一样，AMY-1被发现在体内和体外与AKAP 95的RII结合区结合，并与RII形成三元复合物。还发现AMY-1与AKAP 84/95和RII的复合物的形成阻止催化亚基与该AKAP复合物结合，导致PKA活性的抑制。这些发现表明AMY-1是PKA的重要调节剂。
We have reported that a novel c-Myc-binding protein, AMY-1, binds to cAMP-dependent protein kinase-anchoring protein 149 (AKAP149) and its splicing variant, AKAP84 and is localized in the mitochondria in a complex with RII, a regulatory subunit of cAMP-dependent protein kinase (PKA) (Furusawa, M., Ohnishi, T., Taira, T., Iguchi-Ariga, S. M. M., and Axiga, H. (2001) J. Biol. Chem. 276, 36647-36651). In this study, we further found that AMY-1 competitively bound to either AKAP95 or AKAP84 in the nucleus and the cytoplasm, respectively, in a concentration-dependent manner of either AKAP. Like AKAP84, AMY-1 was found to bind to the RII-binding region of AKAP95 in vivo and in vitro and to make a ternary complex with RII. It was also found that the formation of the complex of AMY-1 with AKAP84/95 and RII prevented a catalytic subunit from binding to this AKAP complex, leading to suppression of PKA activity. These findings suggest that AMY-1 is an important modulator of PKA.