title: Phosphorylation-dependent interaction of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein (YWHA) with PADI6 following oocyte maturation in mice.
abstract: Proteins in the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein family (YWHA; also known as 14-3-3) are involved in the regulation of many intracellular processes. We have examined the interaction of YWHA with peptidylarginine deiminase type VI (PADI6), an abundant protein in mammalian oocytes, eggs, and early embryos. Peptidylarginine deiminases catalyze the posttranslational modification of peptidylarginine to citrulline. PADI6 is associated with oocyte cytoplasmic sheets, and PADI6-deficient mice are infertile because of disruption of development beyond the two-cell stage. We found that PADI6 undergoes a dramatic developmental change in phosphorylation during oocyte maturation. This change in phosphorylation is linked to an interaction of PADI6 with YWHA in the mature egg. Recombinant glutathione S-transferase YWHA pull-down experiments and transgenic tandem affinity purification with liquid chromatography-mass spectrometry demonstrate a binding interaction between YWHA and PADI6 in mature eggs. YWHA proteins modulate or complement intracellular events involving phosphorylation-dependent switching or protein modification. These results indicate that phosphorylation and/or YWHA binding may serve as a means of intracellular PADI6 regulation.
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, Ohio 44242, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Snow
authors.forename: Pawan
authors.initials: P
authors.lastname: Puri
authors.forename: Amparo
authors.initials: A
authors.lastname: Acker-Palmer
authors.forename: Tewis
authors.initials: T
authors.lastname: Bouwmeester
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Vijayaraghavan
authors.forename: Douglas
authors.initials: D
authors.lastname: Kline
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005260:Female; D006867:Hydrolases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008969:Molecular Sequence Data; D009865:Oocytes / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D009866:Oogenesis / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D000080065:Protein-Arginine Deiminase Type 6; D000076342:Protein-Arginine Deiminases; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D006867:Hydrolases; D000080065:Protein-Arginine Deiminase Type 6; D000076342:Protein-Arginine Deiminases; D014365:Tryptophan Hydroxylase; D014446:Tyrosine 3-Monooxygenase; C523190:PADI6 protein, mouse