beta-Arrestin-dependent activation of Ca(2+)/calmodulin kinase II after beta(1)-adrenergic receptor stimulation.

Journal Article (Journal Article)

Ca(2+)/calmodulin kinase II (CaMKII) plays an important role in cardiac contractility and the development of heart failure. Although stimulation of beta(1)-adrenergic receptors (ARs) leads to an increase in CaMKII activity, the molecular mechanism by which beta(1)-ARs activate CaMKII is not completely understood. In this study, we show the requirement for the beta(1)-AR regulatory protein beta-arrestin as a scaffold for both CaMKII and Epac (exchange protein directly activated by cAMP). Stimulation of beta(1)-ARs induces the formation of a beta-arrestin-CaMKII-Epac1 complex, allowing its recruitment to the plasma membrane, whereby interaction with cAMP leads to CaMKII activation. beta-Arrestin binding to the carboxyl-terminal tail of beta(1)-ARs promotes a conformational change within beta-arrestin that allows CaMKII and Epac to remain in a stable complex with the receptor. The essential role for beta-arrestin and identification of the molecular mechanism by which only beta(1)-ARs and not beta(2)-ARs activate CaMKII significantly advances our understanding of this important cellular pathway.

Full Text

Duke Authors

Cited Authors

  • Mangmool, S; Shukla, AK; Rockman, HA

Published Date

  • May 3, 2010

Published In

Volume / Issue

  • 189 / 3

Start / End Page

  • 573 - 587

PubMed ID

  • 20421423

Pubmed Central ID

  • PMC2867304

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

Digital Object Identifier (DOI)

  • 10.1083/jcb.200911047


  • eng

Conference Location

  • United States