High affinity calmodulin target sequence in the signalling molecule PI 3‐kinase

FEBS Letters

Fischer, Roland¹  Julsgart, Juanitta¹  Berchtold, Martin W¹ 

[1] Institute of Molecular Cell Biology, University of Copenhagen, Oster Farimagsgade 2A, 1353 Copenhagen K, Denmark

关键词: Calcium;    Calmodulin;    Phosphatidylinositol 3-kinase;    Signal transduction;   

DOI  :  10.1016/S0014-5793(98)00225-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 p110γ 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.

【 授权许可】

Unknown