title: Evidence for the phosphorylation of serine259 of histone deacetylase 5 by protein kinase Cδ.
abstract: Signaling via pro-growth G protein coupled receptors triggers phosphorylation of HDAC5 on two serine residues (Ser₂₅₉ and Ser₄₉₈), resulting in nuclear export of HDAC5 and de-repression of downstream target genes. In the previous paper we reported the important role of PKD isozymes in the regulation of HDAC5 by phosphorylating Ser₄₉₈ of HDAC5 [Q.K. Huynh, T.A. Mckinsey, Arch. Biochem. Biophys. 450 (2006) 141-148]. In the present paper, we provide evidence that PKCδ can directly phosphorylate Ser₂₅₉ of HDAC5. The evidence is based on the following facts (a) isolated kinase fraction from human failing heart tissues contained PKCδ that phosphorylated HDAC5 Ser₂₅₉ peptide and no significant activity was found for the unbound fraction after they were immunoprecipitated with PKCδ specific antibody; (b) specific inhibitors for PKCδ inhibited kinase activity from isolated fraction and recombinant human PKCδ with similar IC₅₀ values; (c) recombinant human PKCδ can directly phosphorylate full length Ser₂₅₉ HDAC5 protein and HDAC5 Ser₂₅₉ peptide. The results suggest that in addition to activation of protein kinase D isozymes by phosphorylating Ser₇₄₄ and Ser₇₄₈ at their activation sites, PKCδ may also play a role in the regulation of HDAC5 by phosphorylation of Ser₂₅₉.
authors.affiliation: Research and Development, Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, Building 344 Room # 1145, USA. khai.huynh@gilead.com
authors.forename: Q Khai
authors.initials: QK
authors.lastname: Huynh
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D006333:Heart Failure / Q000201:enzymology; D006655:Histone Deacetylases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D012694:Serine; D051745:Protein Kinase C-delta; C404500:HDAC5 protein, human; D006655:Histone Deacetylases