Furusawa Makoto, Taira Takahiro, Iguchi-Ariga Sanae M M, Ariga Hiroyoshi
Graduate School of Pharmaceutical Sciences, College of Medical Technology, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
J Biol Chem. 2002 Dec 27;277(52):50885-92. doi: 10.1074/jbc.M206387200. Epub 2002 Oct 31.
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 Ariga, 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.
我们曾报道过一种新型的c-Myc结合蛋白AMY-1，它可与环磷酸腺苷依赖性蛋白激酶锚定蛋白149（AKAP149）及其剪接变体AKAP84结合，并与环磷酸腺苷依赖性蛋白激酶（PKA）的调节亚基RII形成复合物定位于线粒体中（古泽，M.，大西，T.，平良，T.，井口有贺，S.M.M.，及有贺，H.（2001年）《生物化学杂志》276，36647 - 36651）。在本研究中，我们进一步发现，AMY-1分别在细胞核和细胞质中以浓度依赖性方式竞争性结合AKAP95或AKAP84。与AKAP84类似，发现AMY-1在体内和体外均能与AKAP95的RII结合区域结合，并与RII形成三元复合物。还发现AMY-1与AKAP84/95和RII形成的复合物阻止催化亚基与该AKAP复合物结合，从而导致PKA活性受到抑制。这些发现表明AMY-1是PKA的重要调节因子。
