title: Female infertility in PDE3A(-/-) mice: polo-like kinase 1 (Plk1) may be a target of protein kinase A (PKA) and involved in meiotic arrest of oocytes from PDE3A(-/-) mice.
abstract: Mechanisms of cAMP/PKA-induced meiotic arrest in oocytes are not completely identified. In cultured, G2/M-arrested PDE3A(-/-) murine oocytes, elevated PKA activity was associated with inactivation of Cdc2 and Plk1, and inhibition of phosphorylation of histone H3 (S10) and of dephosphorylation of Cdc25B (S323) and Cdc2 (Thr14/Tyr15). In cultured WT oocytes, PKA activity was transiently reduced and then increased to that observed in PDE3A(-/-) oocytes; Cdc2 and Plk1 were activated, phosphorylation of histone H3 (S10) and dephosphorylation of Cdc25B (S323) and Cdc2 (Thr14/Tyr15) were observed. In WT oocytes, PKAc were rapidly translocated into nucleus, and then to the spindle apparatus, but in PDE3A(-/-) oocytes, PKAc remained in the cytosol. Plk1 was reactivated by incubation of PDE3A(-/-) oocytes with PKA inhibitor, Rp-cAMPS. PDE3A was co-localized with Plk1 in WT oocytes, and co-immunoprecipitated with Plk1 in WT ovary and Hela cells. PKAc phosphorylated rPlk1 and Hela cell Plk1 and inhibited Plk1 activity in vitro. Our results suggest that PKA-induced inhibition of Plk1 may be critical in oocyte meiotic arrest and female infertility in PDE3A(-/-) mice.
authors.affiliation: Translational Medicine Branch (TMB), National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Weixing
authors.initials: W
authors.lastname: Shen
authors.forename: Faiyaz
authors.initials: F
authors.lastname: Ahmad
authors.forename: Steven
authors.initials: S
authors.lastname: Hockman
authors.forename: John
authors.initials: J
authors.lastname: Ma
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Omi
authors.forename: Nalini
authors.initials: N
authors.lastname: Raghavachari
authors.forename: Vincent
authors.initials: V
authors.lastname: Manganiello
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000032:analysis / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1 / Q000378:metabolism; D005260:Female; D016195:G2 Phase; D005838:Genotype; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007247:Infertility, Female / Q000201:enzymology* / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000201:enzymology* / Q000254:growth & development / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020687:cdc25 Phosphatases / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D056744:Cyclin B1; D006657:Histones; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D020687:cdc25 Phosphatases; D000097869:Polo-Like Kinase 1; C517006:Cdc25b protein, mouse; C517289:Pde3a protein, mouse