Protein Kinase B/Akt Phosphorylation of PDE3A and Its Role in Mammalian Oocyte Maturation

EMBO J. 2006 Dec 13;25(24):5716-25. doi: 10.1038/sj.emboj.7601431. Epub 2006 Nov 23.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / chemistry
  • 3',5'-Cyclic-AMP Phosphodiesterases / deficiency
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Enzyme Activation / drug effects
  • Female
  • Humans
  • Insulin / pharmacology
  • Isoenzymes / metabolism
  • Maturation-Promoting Factor / metabolism
  • Mice
  • Molecular Sequence Data
  • Oocytes / cytology*
  • Oocytes / drug effects
  • Oogenesis / drug effects
  • Oogenesis / physiology*
  • Phenotype
  • Phosphorylation / drug effects
  • Phosphoserine / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Xenopus

Substances

  • Insulin
  • Isoenzymes
  • Phosphoserine
  • Proto-Oncogene Proteins c-akt
  • Cyclic AMP-Dependent Protein Kinases
  • Maturation-Promoting Factor
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • PDE3A protein, human
  • Pde3a protein, mouse