High Affinity Calmodulin Target Sequence in the Signalling Molecule PI 3-kinase

FEBS Lett. 1998 Mar 20;425(1):175-7. doi: 10.1016/s0014-5793(98)00225-7.

Abstract

In this study we report that phosphatidylinositol 3-kinase (PI 3-kinase), a lipid kinase which participates in downstream signalling events of heterotrimeric G protein-coupled receptors and receptor tyrosine kinases, contains a high affinity binding site for calmodulin (CaM). The putative CaM-binding peptide derived from the p110gamma isoform interacts with CaM in a calcium-dependent way. Using gel shift analysis and fluorescence spectrophotometry we discovered that the peptide forms a high affinity complex with CaM. Titration experiments using dansylated CaM gave an affinity constant of 5 nM. Furthermore, a sequence comparison among different PI 3-kinase isoforms revealed that the sequence which can bind CaM is highly conserved within different PI 3-kinase isoforms. These results indicate a novel mechanism for regulating PI 3-kinase and provide a new direct link between Ca2+ and phospholipid signalling pathways.

MeSH terms

  • Amino Acid Sequence
  • Calcium / metabolism
  • Calmodulin / metabolism*
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Substrate Specificity

Substances

  • Calmodulin
  • Phosphatidylinositol 3-Kinases
  • Calcium