Linked Life Data

2779522

Source:http://linkedlifedata.com/resource/pubmed/id/2779522

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1989-10-26
pubmed:abstractText
Protein kinase C (PKC) is a Ca2+- and phospholipid-dependent protein kinase that appears to play a critical role in the regulation of cell growth. Melittin was previously shown to inhibit Ca2+- and phosphatidylserine (PS)-dependent PKC activity with an inhibitory potency that was reduced as the PS concentration was elevated. In this report, we found that melittin could inhibit activation of PKC by Ca2+ and PS, with an IC50 of 3 microM. When the enzyme activity was released from regulation by Ca2+ and PS by the generation of an active catalytic fragment of PKC through limited proteolysis, melittin inhibited the enzyme activity with an IC50 of 25 microM. Through inhibitor binding studies and enzyme kinetics, we established that melittin binds directly to the catalytic domain of PKC and that the substrate MgATP can release bound melittin from PKC. Melittin bound to PKC in the absence of PKC cofactors, and MgATP completely disrupted the binding of melittin to PKC, whereas phosphoacceptor substrates did not. The catalytic fragment of PKC, which contains two potential ATP-binding sites according to sequence analysis of PKC-encoding cDNAs, also bound melittin. The kinetics of inhibition of the catalytic fragment were consistent with a noncompetitive inhibition with respect to the substrate ATP, providing evidence that the antagonism of the binding of melittin to PKC by MgATP is not due to a direct competition between MgATP and melittin at the active site of PKC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
355-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
ATP-sensitive binding of melittin to the catalytic domain of protein kinase C.
pubmed:affiliation
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't