Crosstalk between signaling pathways of adrenoreceptors and signal transducers and activators of transcription 3(STAT3)in heart  

作　　者：Kai-zheng GONG Hui ZHANG Jian-hai DU You-yi ZHANG 

机构地区：[1]Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100083, China

出　　处：《Acta Pharmacologica Sinica》2007年第2期153-165,共13页中国药理学报（英文版）

基　　金：grants from the National Key Basic Research Program of People's Republic of China (2006CB503806);the National Natural Science Foundation of China (No_ 30470691 and 30570716); the Research Fund for the Doctoral Program of Higher Education (No 20030001014).

摘　　要：Recently, there have been important advancements in our understanding of the signaling mechanisms of adrenoreceptors （AR） and signal transducers and activators of transcription 3 （STAT3）. While their crucial roles in the pathological processes of the heart are well established, accumulating evidence suggests there is a complex pattern of crosstalk between these 2 signaling pathways. Moreover, the potential for crosstalk occurs at multiple levels in each signaling cascade and involves receptor transactivation, G proteins, small GTPases, cyclic adenosine 3＇, 5＇-monophosphate/protein kinase A, protein kinase C, scaffold/adaptor proteins, protein tyrosine kinases, and mitogen-activated protein kinases. In addition, posttranslational modification （eg acetylation） of STAT3 may provide a link between STAT3 and AR signaling. In particular, crosstalk between these 2 systems in the heart would appear to be dependent upon the species/tissue studied, developmental stage, and eliciting stimulus. This at least partly accounts for the epigenetic effects on biological function that is mediated by the 2 signaling pathways. Elucidation of these mechanisms will provide new targets in the development of novel clinical strategies for heart disorders.Recently, there have been important advancements in our understanding of the signaling mechanisms of adrenoreceptors （AR） and signal transducers and activators of transcription 3 （STAT3）. While their crucial roles in the pathological processes of the heart are well established, accumulating evidence suggests there is a complex pattern of crosstalk between these 2 signaling pathways. Moreover, the potential for crosstalk occurs at multiple levels in each signaling cascade and involves receptor transactivation, G proteins, small GTPases, cyclic adenosine 3＇, 5＇-monophosphate/protein kinase A, protein kinase C, scaffold/adaptor proteins, protein tyrosine kinases, and mitogen-activated protein kinases. In addition, posttranslational modification （eg acetylation） of STAT3 may provide a link between STAT3 and AR signaling. In particular, crosstalk between these 2 systems in the heart would appear to be dependent upon the species/tissue studied, developmental stage, and eliciting stimulus. This at least partly accounts for the epigenetic effects on biological function that is mediated by the 2 signaling pathways. Elucidation of these mechanisms will provide new targets in the development of novel clinical strategies for heart disorders.

关 键 词：RECEPTORS ADRENERGIC signal transduction STAT3 transcription factor HEART 

分 类 号：R331.31[医药卫生—人体生理学] R541.01[医药卫生—基础医学]