首页> 美国卫生研究院文献>Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease >AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP‐Dependent Signaling Pathways in the Heart and Various Signaling Systems
【2h】

AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP‐Dependent Signaling Pathways in the Heart and Various Signaling Systems

机译:Akap12信令复合体:统计依赖性信令途径在心脏和各种信令系统中的影响

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Heart failure is a complex clinical syndrome, represented as an impairment in ventricular filling and myocardial blood ejection. As such, heart failure is one of the leading causes of death in the United States. With a mortality rate of 1 per 8 individuals and a prevalence of 6.2 million Americans, it has been projected that heart failure prevalence will increase by 46% by 2030. Cardiac remodeling (a general determinant of heart failure) is regulated by an extensive network of intertwined intracellular signaling pathways. The ability of signalosomes (molecular signaling complexes) to compartmentalize several cellular pathways has been recently established. These signalosome signaling complexes provide an additional level of specificity to general signaling pathways by regulating the association of upstream signals with downstream effector molecules. In cardiac myocytes, the AKAP12 (A‐kinase anchoring protein 12) scaffolds a large signalosome that orchestrates spatiotemporal signaling through stabilizing pools of phosphatases and kinases. Predominantly upon β‐AR (β2‐adrenergic‐receptor) stimulation, the AKAP12 signalosome is recruited near the plasma membrane and binds tightly to β‐AR. Thus, one major function of AKAP12 is compartmentalizing PKA (protein kinase A) signaling near the plasma membrane. In addition, it is involved in regulating desensitization, downregulation, and recycling of β‐AR. In this review, the critical roles of AKAP12 as a scaffold protein in mediating signaling downstream GPCRs (G protein–coupled receptor) are discussed with an emphasis on its reported and potential roles in cardiovascular disease initiation and progression.
机译:心力衰竭是一种复杂的临床综合征,作为心室填充和心肌血液喷射的损伤。因此,心力衰竭是美国的主要死因之一。每8人的死亡率为1,患有620万美国人的患病率,预计心力衰竭患病率将增加46%到2030年。心脏重塑(心力衰竭的一般决定因素)由广泛的网络调节交织在线的细胞内信号传导途径。最近已建立了误导性(分子信号络合物)对分隔几种细胞途径的能力。这些信号组信号配合物通过调节与下游效应分子的上游信号的关联来提供额外的特异性对一般信号传导途径。在心脏肌细胞中,Akap12(A-激酶锚固蛋白12)支架是一种大型信号,通过稳定磷酸酶和激酶储存来衡量时尚信号传导。主要在β-ar(β2-肾上腺素能受体)刺激上,Akap12信号组在质膜附近招募并将其紧密结合至β-AR。因此,AKAP12的一个主要功能是在质膜附近的分隔率PKA(蛋白激酶A)信号传导。此外,它涉及调节β-AR的脱敏,下调和再循环。在该评论中,AKAP12作为支架蛋白在介导信号传导下游GPCR(G蛋白偶联受体)中的关键作用被讨论,重点是其报告的心血管疾病引发和进展中的潜在作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号