Article
- The EMBO Journal (2006) 25, 5716 - 5725
- doi:10.1038/sj.emboj.7601431
Published online: 23 November 2006
Subject Categories:
Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation
Seung Jin Han1,ab, Sergio Vaccari1,ab, Taku Nedachi2, Carsten B Andersen3, Kristina S Kovacina4, Richard A Roth4 and Marco Conti1
- Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA
- Tohoku University Biomedical Engineering Research Organization, Sendai, Japan
- Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA
- Department of Molecular Pharmacology, Stanford University, Stanford, CA, USA
Correspondence to:
Marco Conti, Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University, 300 Pasteur dr., Stanford, CA 94305, USA. Tel.: +1 650 725 2452; Fax: +1 650 725 7102; E-mail: Marco.conti@stanford.edu
aThese authors contributed equally to this work
bRecipients of a fellowship from the Lalor Foundation
Received 16 June 2006; Accepted 19 October 2006
Abstract
cGMP-inhibited cAMP phosphodiesterase 3A (PDE3A) is expressed in mouse oocytes, and its function is indispensable for meiotic maturation as demonstrated by genetic ablation. Moreover, PDE3 activity is required for insulin/insulin-like growth factor-1 stimulation of Xenopus oocyte meiotic resumption. Here, we investigated the cAMP-dependent protein kinase B (PKB)/Akt regulation of PDE3A and its impact on oocyte maturation. Cell-free incubation of recombinant mouse PDE3A with PKB/Akt or cAMP-dependent protein kinase A catalytic subunits leads to phosphorylation of the PDE3A protein. Coexpression of PDE3A with constitutively activated PKB/Akt (Myr-Akt) increases PDE activity as well as its phosphorylation state. Injection of pde3a mRNA potentiates insulin-dependent maturation of Xenopus oocytes and rescues the phenotype of pde3-/- mouse oocytes. This effect is greatly decreased by mutation of any of the PDE3A serines 290–292 to alanine in both Xenopus and mouse. Microinjection of myr-Akt in mouse oocytes causes in vitro meiotic maturation and this effect requires PDE3A. Collectively, these data indicate that activation of PDE3A by PKB/Akt-mediated phosphorylation plays a role in the control of PDE3A activity in mammalian oocytes.
Keywords:
- oocyte maturation,
- PDE3A,
- PKB/Akt,
- phosphorylation



