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High affinity calmodulin target sequence in the signalling molecule PI 3‐kinase
Author(s) -
Fischer Roland,
Julsgart Juanitta,
Berchtold Martin W
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00225-7
Subject(s) - calmodulin , biochemistry , gene isoform , kinase , phosphatidylinositol , tyrosine kinase , biology , heterotrimeric g protein , pi , chemistry , signal transduction , microbiology and biotechnology , enzyme , g protein , gene
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 Ca 2+ and phospholipid signalling pathways.