PKA-mediated phosphorylation of the beta1-adrenergic receptor promotes Gs/Gi switching.

Journal Article (Journal Article)

Recently, it has been shown that PKA-mediated phosphorylation of the beta(2)-adrenergic receptor (beta(2)-AR) by the cyclic AMP-dependent protein kinase (PKA) reduces its affinity for G(s) and increases its affinity for G(i). Here we demonstrate that, like the beta(2)-AR, the beta(1)-AR is also capable of "switching" its coupling from G(s) to G(i) in a PKA-dependent manner. The beta(1)-AR is capable of activating adenylate cyclase via G(s), and can also activate the extracellular-regulated kinases, p44 and p42 (ERK1/2). In transfected CHO cells, the observed beta(1)-AR-mediated activation of ERK is both sensitive to pertussis toxin (PTX), indicating involvement of G(i)/G(o), and to the PKA inhibitor, H-89. beta(1)-ARs with PKA phosphorylation sites mutated to alanines are unable to activate ERK. Mutating these same residues to aspartic acid, mimicking PKA phosphorylation, leads to a decrease in G(s)-stimulated cAMP accumulation and an increase in PTX-sensitive ERK activation. These results strongly support the hypothesis that the beta(1)-AR, like the beta(2)-AR, can undergo PKA-dependent "G(s)/G(i) switching".

Full Text

Duke Authors

Cited Authors

  • Martin, NP; Whalen, EJ; Zamah, MA; Pierce, KL; Lefkowitz, RJ

Published Date

  • December 2004

Published In

Volume / Issue

  • 16 / 12

Start / End Page

  • 1397 - 1403

PubMed ID

  • 15381255

International Standard Serial Number (ISSN)

  • 0898-6568

Digital Object Identifier (DOI)

  • 10.1016/j.cellsig.2004.05.002


  • eng

Conference Location

  • England