Sphingosylphosphorylcholine as a novel calmodulin inhibitor

Erika Kovacs, Karoly Liliom

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

S1P (sphingosine 1-phosphate) and SPC (sphingosylphosphorylcholine) have been recently recognized as important mediators of cell signalling, regulating basic cellular processes such as growth, differentiation, apoptosis, motility and Ca2+ homoeostasis. Interestingly, they can also act as first and second messengers. Although their activation of cell-surface G-protein-coupled receptors has been studied extensively, not much is known about their intracellular mechanism of action, and their target proteins are yet to be identified. We hypothesized that these sphingolipids might bind to CaM (calmodulin), the ubiquitous intracellular Ca2+ sensor. Binding assays utilizing intrinsic tyrosine fluorescence of the protein, dansyl-labelled CaM and surface plasmon resonance revealed that SPC binds to both apo- and Ca2+-saturated CaM selectively, when compared with the related lysophospholipid mediators S1P, LPA (lysophosphatidic acid) and LPC (lysophosphatidylcholine). Experiments carried out with the model CaM-binding domain melittin showed that SPC dissociates the CaM-target peptide complex, suggesting an inhibitory role. The functional effect of the interaction was examined on two target enzymes, phosphodiesterase and calcineurin, and SPC inhibited the Ca2+/CaM-dependent activity of both. Thus we propose that CaM might be an intracellular receptor for SPC, and raise the possibility of a novel endogenous regulation of CaM.

Original languageEnglish
Pages (from-to)427-437
Number of pages11
JournalBiochemical Journal
Volume410
Issue number2
DOIs
Publication statusPublished - Mar 1 2008

Keywords

  • Calmodulin
  • Intracellular receptor
  • Second messenger
  • Sphingosine 1-phosphate
  • Sphingosylphosphorylcholine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Sphingosylphosphorylcholine as a novel calmodulin inhibitor'. Together they form a unique fingerprint.

  • Cite this