Abstract
Signaling via pro-growth G protein coupled receptors triggers phosphorylation of HDAC5 on two serine residues (Ser&sub2;₅₉ and Ser&sub4;₉₈), 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 Ser&sub4;₉₈ 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 Ser&sub2;₅₉ of HDAC5. The evidence is based on the following facts (a) isolated kinase fraction from human failing heart tissues contained PKCδ that phosphorylated HDAC5 Ser&sub2;₅₉ 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 IC₅&sub0; values; (c) recombinant human PKCδ can directly phosphorylate full length Ser&sub2;₅₉ HDAC5 protein and HDAC5 Ser&sub2;₅₉ peptide. The results suggest that in addition to activation of protein kinase D isozymes by phosphorylating Ser₇&sub4;&sub4; and Ser₇&sub4;₈ at their activation sites, PKCδ may also play a role in the regulation of HDAC5 by phosphorylation of Ser&sub2;₅₉.