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

R Fischer; J Julsgart; M W Berchtold

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

R Fischer, J Julsgart, M W Berchtold

Cell Biology and Physiology

41 Citations (Scopus)

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.

Original language	English
Journal	FEBS Letters
Volume	425
Issue number	1
Pages (from-to)	175-7
Number of pages	2
ISSN	0014-5793
Publication status	Published - 1998

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title = "High affinity calmodulin target sequence in the signalling molecule PI 3-kinase",

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.",

author = "R Fischer and J Julsgart and Berchtold, {M W}",

note = "Keywords: 1-Phosphatidylinositol 3-Kinase; Amino Acid Sequence; Calcium; Calmodulin; Molecular Sequence Data; Sequence Homology, Amino Acid; Signal Transduction; Substrate Specificity",

year = "1998",

language = "English",

volume = "425",

pages = "175--7",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "JohnWiley & Sons Ltd",

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TY - JOUR

T1 - High affinity calmodulin target sequence in the signalling molecule PI 3-kinase

AU - Fischer, R

AU - Julsgart, J

AU - Berchtold, M W

N1 - Keywords: 1-Phosphatidylinositol 3-Kinase; Amino Acid Sequence; Calcium; Calmodulin; Molecular Sequence Data; Sequence Homology, Amino Acid; Signal Transduction; Substrate Specificity

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 9541031

SN - 0014-5793

VL - 425

SP - 175

EP - 177

JO - FEBS Letters

JF - FEBS Letters

IS - 1

ER -

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

Abstract

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