title: Golgi apparatus casein kinase phosphorylates bioactive Ser-6 of bone morphogenetic protein 15 and growth and differentiation factor 9.
abstract: Bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9 (GDF-9) are oocyte-secreted factors that play essential roles in human folliculogenesis and ovulation. Their bioactivity is tightly regulated through phosphorylation, likely to occur within the Golgi apparatus of the secretory pathway. Here we show that Golgi apparatus casein kinase (G-CK) catalyzes the phosphorylation of rhBMP-15 and rhGDF-9. rhBMP-15, in particular, is an excellent substrate for G-CK. In each protein a single residue is phosphorylated by G-CK, corresponding to the serine residue at the sixth position of the mature region of both rhBMP-15 and rhGDF-9, whose phosphorylation is required for biological activity.
authors.affiliation: Department of Biological Chemistry, University of Padova, Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tibaldi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arrigoni
authors.forename: Heather M
authors.initials: HM
authors.lastname: Martinez
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inagaki
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shimasaki
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Pinna
mesh_terms: D000818:Animals; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics / Q000378:metabolism*; D047388:Casein Kinases / Q000378:metabolism*; D002384:Catalysis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006056:Golgi Apparatus / Q000201:enzymology*; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008321:Mammary Glands, Animal / Q000201:enzymology; D013058:Mass Spectrometry; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D055430:Bone Morphogenetic Protein 15; D055429:Growth Differentiation Factor 9; D011994:Recombinant Proteins; D012694:Serine; D047388:Casein Kinases; D019311:Staurosporine