Linked Life Data

16584705

Source:http://linkedlifedata.com/resource/pubmed/id/16584705

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-6-13
pubmed:abstractText
Class II histone deacetylases (HDACs) are signal-responsive repressors of gene transcription. In the heart, class II HDAC5 suppresses expression of genes that govern stress-induced cardiomyocyte growth. Signaling via pro-growth G protein coupled receptors triggers phosphorylation of HDAC5 on two serine residues (Ser(259) and Ser(498)), resulting in nuclear export of HDAC5 and de-repression downstream target genes. Although prior studies established a role for protein kinase D (PKD) in the regulation of HDAC5 phosphorylation, it remained unclear whether PKD functions directly or indirectly to control the phosphorylation status of this transcriptional repressor. Here, we demonstrate that PKD catalyzes direct phosphoryl-group transfer to Ser(498) of HDAC5. Each of the three PKD family members, PKD1, PKD2, and PKD3, is capable of phosphorylating HDAC5 (K(m) for substrate=2.07, 3.12, and 1.43microM, respectively), although PKD2 exhibits highest catalytic efficiency (k(cat)/K(m)=6.77min(-1)microM(-1)). Kinetic studies revealed that the three PKD isozymes phosphorylate HDAC5 through a random sequential mechanism, and that ATP has no effect on association of kinase with peptide substrate. In addition, we demonstrate that ADP competitively inhibits phosphorylation of HDAC5 (K(i)=8.50, 17.54, and 11.98microM for PKD1, PKD2, and PKD3, respectively). These findings define PKD as an HDAC kinase and thus suggest key roles for PKD family members in the control of chromatin structure and gene expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
450
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
141-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Protein kinase D directly phosphorylates histone deacetylase 5 via a random sequential kinetic mechanism.
pubmed:affiliation
Research and Development, Myogen, Inc., 7575 West 103(rd) Ave., Westminster, CO 80021, USA. khai.huynh@myogen.com
pubmed:publicationType
Journal Article