Connexin43 phosphorylation: structural changes and biological effects.

Connexin43 phosphorylation: structural changes and biological effects.
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DOI:
10.1042/bj20082319
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发表时间:
2009-04-15
期刊:
The Biochemical journal
影响因子:
--
通讯作者:
Lampe PD
Lampe PD
中科院分区:
其他
文献类型:
--
作者:
Solan JL;Lampe PD

文献摘要

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脊椎动物间隙连接由连接蛋白基因家族的蛋白质组成,在胚胎发育、可兴奋细胞的协调收缩、组织稳态、正常细胞生长和分化中发挥着关键作用。 Connexin43 是最丰富且普遍表达的连接蛋白,其磷酸化与连接蛋白“生命周期”多个阶段的间隙连接通讯调节有关,包括半通道寡聚、蛋白质向质膜的输出、半通道活性、间隙连接组装、间隙连接通道门控和连接蛋白降解。与短(1−5 小时)的蛋白质半衰期一致,connexin43 磷酸化是动态的,并且会响应许多不同激酶的激活而变化。这篇综述评估了我们目前对磷酸化对 connexin43 结构和功能的影响的理解,这些影响反过来又调节间隙连接生物学,重点是心脏和皮肤中发生的事件。
Vertebrate gap junctions, composed of proteins from the connexin gene family, play critical roles in embryonic development, coordinated contraction of excitable cells, tissue homeostasis, normal cell growth and differentiation. Phosphorylation of connexin43, the most abundant and ubiquitously expressed connexin, has been implicated in the regulation of gap junctional communication at several stages of the connexin “life cycle” including hemichannel oligomerization, export of the protein to the plasma membrane, hemichannel activity, gap junction assembly, gap junction channel gating and connexin degradation. Consistent with a short (1−5 h) protein half-life, connexin43 phosphorylation is dynamic and changes in response to activation of many different kinases. This review assesses our current understanding of the effects of phosphorylation on connexin43 structure and function that in turn regulate gap junction biology with an emphasis on events occurring in heart and skin.