Linked Life Data

17692392

Source:http://linkedlifedata.com/resource/pubmed/id/17692392

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-9-11
pubmed:abstractText
Rottlerin has been used as a protein kinase Cdelta (PKCdelta)-selective inhibitor in hundreds of studies, on the basis of initial substrate phosphorylation studies in vitro. However, in more recent studies, rottlerin did not block PKCdelta activity but did block other kinase and non-kinase proteins in vitro and activated multiple Ca(2+)-sensitive K(+) channels with high potency. Rottlerin uncouples mitochondria, and this uncoupling depolarizes the mitochondrial membrane potential, reduces cellular ATP levels, activates 5'-AMP-activated protein kinase (AMPK) and affects mitochondrial production of reactive oxygen species (ROS). Classical mitochondrial uncouplers also produce these secondary changes, and reductions in ATP can block PKCdelta tyrosine phosphorylation and activation and generate effects resembling those produced by direct inhibition of kinase. Rottlerin also has effects in cells in which PKCdelta is downregulated or genetically deleted. These findings indicate that there have been gross misinterpretations in studies using rottlerin as a pharmacological tool to identify PKCdelta-dependent cellular events and indicate that rottlerin should not be used to determine the involvement of PKCdelta in biological processes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0165-6147
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
453-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Rottlerin: an inappropriate and ineffective inhibitor of PKCdelta.
pubmed:affiliation
Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, New Research Building, Room 1030-J, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. ssoltoff@bidmc.harvard.edu
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural