Linked Life Data

15084589

Source:http://linkedlifedata.com/resource/pubmed/id/15084589

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2004-6-21
pubmed:abstractText
Oxidative stress induced by cell treatments with H(2)O(2) activates protein kinase D (PKD) via a protein kinase C (PKC)-dependent signal transduction pathway (Waldron, R. T., and Rozengurt, E. (2000) J. Biol. Chem. 275, 17114-17121). Here we show that oxidative stress induces PKC-dependent activation loop Ser(744) and Ser(748) phosphorylation to mediate dose- and time-dependent activation of PKD, both endogenously expressed in Swiss 3T3 cells and stably overexpressed in Swiss 3T3-GFP.PKD cells. Although oxidative stress induced PKD activation loop phosphorylation and activation with identical kinetics, both were dose-dependently blocked by preincubation of cells with selective inhibitors of PKC (GF109203X and Gö6983) or c-Src (PP2). Inhibition of Src tyrosine kinase activity eliminated oxidative stress-induced direct PKD tyrosine phosphorylation, but only partially attenuated activation loop phosphorylation and activation. Mutation of a putative tyrosine phosphorylation site on PKD, Tyr(469) to phenylalanine, had no effect on its activation by oxidative stress in transfected COS-7 cells. Similarly, a mutant with Tyr(469) replaced by aspartic acid had increased basal activity but was also further activated by oxidative stress. Thus, PKD tyrosine phosphorylation at this site neither produced full activation by itself nor was required for oxidative stress-induced activation mediated by activation loop phosphorylation. In addition to PKD activation, activation loop phosphorylation in response to oxidative stress also redistributed activated PKD to cell nuclei, as revealed by PKD indirect immunofluorescence, imaging of a PKD-green fluorescent protein fusion construct (GFP-PKD), and analysis of nuclear pellets. Cell preincubation with Gö6983 strongly diminished H(2)O(2)-induced nuclear relocalization of GFP-PKD. Taken together, these results indicate that PKC-mediated PKD Ser(744) and Ser(748) phosphorylation induced by oxidative stress integrates PKD activation with redistribution to the nucleus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27482-93
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15084589-Acetylcysteine, pubmed-meshheading:15084589-Amino Acid Substitution, pubmed-meshheading:15084589-Animals, pubmed-meshheading:15084589-COS Cells, pubmed-meshheading:15084589-Cell Nucleus, pubmed-meshheading:15084589-Cercopithecus aethiops, pubmed-meshheading:15084589-Enzyme Activation, pubmed-meshheading:15084589-Mice, pubmed-meshheading:15084589-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:15084589-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:15084589-Mitogen-Activated Protein Kinases, pubmed-meshheading:15084589-Oxidative Stress, pubmed-meshheading:15084589-Phosphorylation, pubmed-meshheading:15084589-Protein Kinase C, pubmed-meshheading:15084589-Recombinant Proteins, pubmed-meshheading:15084589-Serine, pubmed-meshheading:15084589-Signal Transduction, pubmed-meshheading:15084589-Swiss 3T3 Cells, pubmed-meshheading:15084589-Transfection, pubmed-meshheading:15084589-Tyrosine
pubmed:year
2004
pubmed:articleTitle
Oxidative stress induces protein kinase C-mediated activation loop phosphorylation and nuclear redistribution of protein kinase D.
pubmed:affiliation
Division of Digestive Diseases, Department of Medicine, UCLA David Geffen School of Medicine, UCLA-CURE Digestive Diseases Research Center and Molecular Biology Institute, UCLA, Los Angeles, California 90095-1786, USA. rwaldron@mednet.ucla.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.