Journal of Biological Chemistry
Volume 283, Issue 48, 28 November 2008, Pages 33527-33535
Journal home page for Journal of Biological Chemistry

Mechanisms of Signal Transduction
Adenylyl Cyclase Type VI Increases Akt Activity and Phospholamban Phosphorylation in Cardiac Myocytes*

https://doi.org/10.1074/jbc.M805825200Get rights and content
Under a Creative Commons license
open access

Increased expression of adenylyl cyclase VI has beneficial effects on the heart, but strategies that increase cAMP production in cardiac myocytes usually are harmful. Might adenylyl cyclase VI have beneficial effects unrelated to increased β-adrenergic receptor-mediated signaling? We previously reported that adenylyl cyclase VI reduces cardiac phospholamban expression. Our focus in the current studies is how adenylyl cyclase VI influences phospholamban phosphorylation. In cultured cardiac myocytes, increased expression of adenylyl cyclase VI activates Akt by phosphorylation at serine 473 and threonine 308 and is associated with increased nuclear phospho-Akt. Activated Akt phosphorylates phospholamban, a process that does not require β-adrenergic receptor stimulation or protein kinase A activation. These previously unrecognized signaling events would be predicted to promote calcium handling and increase contractile function of the intact heart independently of β-adrenergic receptor activation. We speculate that phospholamban phosphorylation, through activation of Akt, may be an important mechanism by which adenylyl cyclase VI increases the function of the failing heart.

Cited by (0)

*

This work was supported, in whole or in part, by National Institutes of Health Grant 5P01HL066941, HL081741, and HL088426-01 (to H. K. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1

Supported by Grant-In-Aid 0765064Y.

2

Supported by Grant-In-Aid 0865147F from the Western States Affiliate of the American Heart Association.