AKAP12和AKAP5形成高阶异聚物。

Q2 Biochemistry, Genetics and Molecular Biology Journal of Molecular Signaling Pub Date : 2011-08-10 DOI:10.1186/1750-2187-6-8
Shujuan Gao, Hsien-Yu Wang, Craig C Malbon
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引用次数: 19

摘要

背景:a -激酶锚定蛋白家族(AKAPs)是一组分子支架,可催化蛋白激酶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。AKAP5 (MW ~47 kDa)和AKAP12 (MW ~191 kDa)均为寡聚,但这两种akap是否能异聚成复杂性更高的超分子支架尚不清楚。结果:以固定的AKAPs为“诱饵”的亲和色谱明确表明,AKAP5和AKAP12确实形成了最小的异二聚体。对AKAP5和AKAP12混合物进行立体排斥色谱分析,发现两者都含有非常大的超分子复合物。在β -肾上腺素能激动剂刺激下,AKAP5与AKAP12的对接增加了4倍。研究发现,在β -肾上腺素能激动剂刺激下,AKAP12的过表达可增强akap5介导的Erk1/2激活。结论:AKAP5和AKAP12能够形成异聚寡聚的超分子复合物,影响AKAP的定位和功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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AKAP12 and AKAP5 form higher-order hetero-oligomers.

Background: 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.

Results: 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.

Conclusion: AKAP5 and AKAP12 are capable of forming hetero-oligomeric supermolecular complexes that influence AKAP locale and function.

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来源期刊
Journal of Molecular Signaling
Journal of Molecular Signaling Biochemistry, Genetics and Molecular Biology-Biochemistry
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期刊介绍: Journal of Molecular Signaling is an open access, peer-reviewed online journal that encompasses all aspects of molecular signaling. Molecular signaling is an exponentially growing field that encompasses different molecular aspects of cell signaling underlying normal and pathological conditions. Specifically, the research area of the journal is on the normal or aberrant molecular mechanisms involving receptors, G-proteins, kinases, phosphatases, and transcription factors in regulating cell proliferation, differentiation, apoptosis, and oncogenesis in mammalian cells. This area also covers the genetic and epigenetic changes that modulate the signaling properties of cells and the resultant physiological conditions.
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