Coghlan V M, Perrino B A, Howard M, Langeberg L K, Hicks J B, Gallatin W M, Scott J D
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Science. 1995 Jan 6;267(5194):108-11. doi: 10.1126/science.7528941.
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.
蛋白激酶和磷酸酶的特异性可通过与优选底物的区室化来实现。在神经元中，3',5'-环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）通过其调节亚基与A激酶锚定蛋白AKAP79的结合而定位在突触后致密区。相互作用克隆实验表明，AKAP79还结合蛋白磷酸酶2B或钙调神经磷酸酶（CaN）。从牛脑中分离出了PKA、AKAP和CaN的三元复合物，并在培养的海马神经元的神经突中确定了激酶和磷酸酶的共定位。AKAP79的推定CaN结合结构域与亲免蛋白FKBP-12的相似，并且AKAP79抑制CaN磷酸酶活性。这些结果表明，PKA和CaN都通过与共同的锚定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。
