title: Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation.
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.
authors.affiliation: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Sergio
authors.initials: S
authors.lastname: Vaccari
authors.forename: Taku
authors.initials: T
authors.lastname: Nedachi
authors.forename: Carsten B
authors.initials: CB
authors.lastname: Andersen
authors.forename: Kristina S
authors.initials: KS
authors.lastname: Kovacina
authors.forename: Richard A
authors.initials: RA
authors.lastname: Roth
authors.forename: Marco
authors.initials: M
authors.lastname: Conti
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D016200:Maturation-Promoting Factor / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects; D009866:Oogenesis / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014981:Xenopus
chemical_list: D007328:Insulin; D007527:Isoenzymes; D010768:Phosphoserine; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D016200:Maturation-Promoting Factor; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517287:PDE3A protein, human; C517289:Pde3a protein, mouse