AKAP12 and AKAP5 form higher-order hetero-oligomers.
AKAP12 and AKAP5 form higher-order hetero-oligomers.
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DOI：
10.1186/1750-2187-6-8
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发表时间：
2011-08-10
影响因子：
--
通讯作者：
Malbon CC
中科院分区：
文献类型：
--
作者：
Gao S;Wang HY;Malbon CC
A-激酶锚定蛋白（AKAP）家族构成了一组分子支架，其用于催化蛋白激酶A、蛋白激酶C、酪氨酸激酶、G-蛋白偶联受体和离子通道的动态相互作用。AKAP 5（MW ~47 kDa）和AKAP 12（MW ~191 kDa）同源寡聚化，但这种AKAP是否可以异源寡聚化成复杂性增加的超分子支架尚不清楚。使用固定化AKAP作为“诱饵”的亲和层析明确地证明AKAP 5和AKAP 12确实形成最低限度的异源二聚体。AKAP 5和AKAP 12混合物的空间排阻色谱显示存在非常大的，超分子复合物含有AKAP。AKAP 5与AKAP 12的对接通过β-肾上腺素能激动剂刺激增加4倍。AKAP 1/2的过表达被发现增强AKAP 5介导的Erk 1/2激活，以响应β-肾上腺素能激动剂的刺激。AKAP 5和AKAP 12能够形成影响AKAP位置和功能的异源寡聚超分子复合物。
The family of A-kinase-anchoring proteins, AKAPs, constitutes a group of molecular scaffolds that act to catalyze dynamic interactions of protein kinase A, protein kinase C, tyrosine kinases, G-protein-coupled receptors and ion channels. AKAP5 (MW ~47 kDa) and AKAP12 (MW ~191 kDa) homo-oligomerize, but whether or not such AKAPs can hetero-oligomerize into supermolecular scaffolds of increased complexity is unknown. Affinity chromatography using immobilized AKAPs as "bait" demonstrates unequivocally that AKAP5 and AKAP12 do form minimally hetero-dimers. Steric-exclusion chromatography of AKAP5 and AKAP12 mixtures revealed the existence of very large, supermolecular complexes containing both AKAPs. Docking of AKAP5 to AKAP12 was increased 4-fold by beta-adrenergic agonist stimulation. Overexpression of AKAP12 was found to potentiate AKAP5-mediated Erk1/2 activation in response to stimulation with beta-adrenergic agonist. AKAP5 and AKAP12 are capable of forming hetero-oligomeric supermolecular complexes that influence AKAP locale and function.