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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-1-11
pubmed:abstractText
Previously we have identified the lipid mediator sphingosylphosphorylcholine (SPC) as the first potentially endogenous inhibitor of the ubiquitous Ca2+ sensor calmodulin (CaM) (Kovacs, E., and Liliom, K. (2008) Biochem. J. 410, 427-437). Here we give mechanistic insight into CaM inhibition by SPC, based on fluorescence stopped-flow studies with the model CaM-binding domain melittin. We demonstrate that both the peptide and SPC micelles bind to CaM in a rapid and reversible manner with comparable affinities. Furthermore, we present kinetic evidence that both species compete for the same target site on CaM, and thus SPC can be considered as a competitive inhibitor of CaM-target peptide interactions. We also show that SPC disrupts the complex of CaM and the CaM-binding domain of ryanodine receptor type 1, inositol 1,4,5-trisphosphate receptor type 1, and the plasma membrane Ca2+ pump. By interfering with these interactions, thus inhibiting the negative feedback that CaM has on Ca2+ signaling, we hypothesize that SPC could lead to Ca2+ mobilization in vivo. Hence, we suggest that the action of the sphingolipid on CaM might explain the previously recognized phenomenon that SPC liberates Ca2+ from intracellular stores. Moreover, we demonstrate that unlike traditional synthetic CaM inhibitors, SPC disrupts the complex between not only the Ca2+-saturated but also the apo form of the protein and the target peptide, suggesting a completely novel regulation for target proteins that constitutively bind CaM, such as ryanodine receptors.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-10884684, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-11035044, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-11256963, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-11814356, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-11829755, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-11891559, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-11955285, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-12069827, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-12518027, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-12942086, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-1474585, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-1519061, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-15258917, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-15970592, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-16552497, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-17027503, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-17400264, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-17666077, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-17979830, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-18042469, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-18328800, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-1958205, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-2110826, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-2163543, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-2526124, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-6250577, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-6847615, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-7712168, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-7755592, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-8259515, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-8566178, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-8700873, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-8896446, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-9013581, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-9078280, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-9141499, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-9301339, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-9726638, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-9799490, http://linkedlifedata.com/resource/pubmed/commentcorrection/19910470-9972865
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1799-808
pubmed:dateRevised
2011-7-20
pubmed:meshHeading
pubmed-meshheading:19910470-Amino Acid Sequence, pubmed-meshheading:19910470-Animals, pubmed-meshheading:19910470-Apoproteins, pubmed-meshheading:19910470-Binding, Competitive, pubmed-meshheading:19910470-Calcium, pubmed-meshheading:19910470-Calcium Signaling, pubmed-meshheading:19910470-Calmodulin, pubmed-meshheading:19910470-Cattle, pubmed-meshheading:19910470-Humans, pubmed-meshheading:19910470-Intracellular Space, pubmed-meshheading:19910470-Kinetics, pubmed-meshheading:19910470-Melitten, pubmed-meshheading:19910470-Micelles, pubmed-meshheading:19910470-Molecular Sequence Data, pubmed-meshheading:19910470-Phosphorylcholine, pubmed-meshheading:19910470-Protein Structure, Tertiary, pubmed-meshheading:19910470-Ryanodine Receptor Calcium Release Channel, pubmed-meshheading:19910470-Spectrometry, Fluorescence, pubmed-meshheading:19910470-Sphingosine
pubmed:year
2010
pubmed:articleTitle
Dissociation of calmodulin-target peptide complexes by the lipid mediator sphingosylphosphorylcholine: implications in calcium signaling.
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