ASSOCIATION OF PROTEIN-KINASE-A AND PROTEIN-PHOSPHATASE-2B WITH A COMMON ANCHORING PROTEIN
ASSOCIATION OF PROTEIN-KINASE-A AND PROTEIN-PHOSPHATASE-2B WITH A COMMON ANCHORING PROTEIN
复制标题
DOI：
10.1126/science.7528941
复制
发表时间：
1995-01-06
期刊：
影响因子：
56.9
通讯作者：
SCOTT, JD
中科院分区：
文献类型：
--
作者：
COGHLAN, VM;PERRINO, BA;SCOTT, JD
蛋白激酶和磷酸酶的特异性可以通过用优选底物进行区室化来实现。在神经元中，腺苷3 '，5'-单磷酸（cAMP）依赖性蛋白激酶（PKA）通过其调节亚基与A激酶锚蛋白AKAP 79的结合而定位于突触后密度。相互作用克隆实验表明，AKAP 79还结合蛋白磷酸酶2B或钙调神经磷酸酶（CaN）。从牛脑中分离出PKA、AKAP和CaN的三元复合物，并在培养的海马神经元的轴突中建立了激酶和磷酸酶的共定位。AKAP 79的推定CaN结合结构域与亲免素FKBP-12的结构域相似，并且AKAP 79抑制CaN磷酸酶活性。这些结果表明，PKA和CaN都是通过与一个共同的锚蛋白结合而靶向亚细胞位点，从而调节关键神经元底物的磷酸化状态。
Specificity of protein kinases and phosphatases may be achieved through compartmentalization with preferred substrates. In neurons, adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) is localized at postsynaptic densities by association of its regulatory subunit with an A kinase anchor protein, AKAP79. Interaction cloning experiments demonstrated that AKAP79 also binds protein phosphatase 2B, or calcineurin (CaN). A ternary complex of PKA, AKAP, and CaN was isolated from bovine brain, and colocalization of the kinase and the phosphatase was established in neurites of cultured hippocampal neurons. The putative CaN-binding domain of AKAP79 is similar to that of the immunophilin FKBP-12, and AKAP79 inhibited CaN phosphatase activity. These results suggest that both PKA and CaN are targeted to subcellular sites by association with a common anchor protein and thereby regulate the phosphorylation state of key neuronal substrates.