Cardiac function modulation depends on the A-kinase anchoring protein complex

被引:14
作者
Zhu, Yan-Rong [1 ]
Jiang, Xiao-Xin [1 ]
Zheng, Yaguo [1 ]
Xiong, Jing [2 ]
Wei, Dongping [3 ]
Zhang, Dai-Min [1 ]
机构
[1] Nanjing Med Univ, Nanjing Hosp 1, Dept Cardiol, Nanjing 210006, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Dept Pharmacol, Nanjing, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Nanjing Hosp 1, Dept Oncol, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
A-kinase anchoring proteins; arrhythmia; calmodulin; cardiomyocytes; hypertrophy; large-conductance Ca2+-activated K+ channels; sudden cardiac death; KAPPA-B ACTIVATION; AKAP-LBC; ADENYLYL-CYCLASE; SUBCELLULAR-LOCALIZATION; POTASSIUM CHANNEL; CA(V)1.2 CHANNELS; DOWN-REGULATION; VASCULAR-TONE; KNOCKOUT MICE; PKA;
D O I
10.1111/jcmm.14659
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The A-kinase anchoring proteins (AKAPs) are a group of structurally diverse proteins identified in various species and tissues. These proteins are able to anchor protein kinase and other signalling proteins to regulate cardiac function. Acting as a scaffold protein, AKAPs ensure specificity in signal transduction by enzymes close to their appropriate effectors and substrates. Over the decades, more than 70 different AKAPs have been discovered. Accumulative evidence indicates that AKAPs play crucial roles in the functional regulation of cardiac diseases, including cardiac hypertrophy, myofibre contractility dysfunction and arrhythmias. By anchoring different partner proteins (PKA, PKC, PKD and LTCCs), AKAPs take part in different regulatory pathways to function as regulators in the heart, and a damaged structure can influence the activities of these complexes. In this review, we highlight recent advances in AKAP-associated protein complexes, focusing on local signalling events that are perturbed in cardiac diseases and their roles in interacting with ion channels and their regulatory molecules. These new findings suggest that AKAPs might have potential therapeutic value in patients with cardiac diseases, particularly malignant rhythm.
引用
收藏
页码:7170 / 7179
页数:10
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