Phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ), a lipid signalling enigma.
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Authors
Giudici, Maria-Luisa
Clarke, Jonathan H
Irvine, Robin F
Abstract
The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are an important family of enzymes, whose physiological roles are being teased out by a variety of means. Phosphatidylinositol-5-phosphate 4-kinase γ (PI5P4Kγ) is especially intriguing as its in vitro activity is very low. Here we review what is known about this enzyme and discuss some recent advances towards an understanding of its physiology. Additionally, the effects of the ATP-competitive inhibitor I-OMe Tyrphostin AG-538 on all three mammalian PI5P4Ks was explored, including two PI5P4Kγ mutants with altered ATP- or PI5P-binding sites. The results suggest a strategy for targeting non-ATP binding sites on inositol lipid kinases.
Description
Keywords
PI5P, PI5P4K, PI5P4Kγ, Phosphatidylinositol 5-phosphate, Phosphatidylinositol 5-phosphate 4-kinase γ, Adenosine Triphosphate, Animals, Binding Sites, Binding, Competitive, Catechols, Enzyme Inhibitors, Gene Expression, Humans, Isoenzymes, Phosphatidylinositol Phosphates, Phosphotransferases (Alcohol Group Acceptor), Protein Binding, Signal Transduction, Tyrphostins
Journal Title
Adv Biol Regul
Conference Name
Journal ISSN
2212-4926
2212-4934
2212-4934
Volume Title
Publisher
Elsevier BV
Publisher DOI
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/J01575X/1)
Medical Research Council (MR/J001120/1)
Medical Research Council (MR/J001120/1)
We are very grateful to Dr A. Vandewalle (INSERM U773, Paris, France) for provision of the mpkCCD cell line. M.-L.G. was supported by the BBSRC (Grant RG65394) and J.H.C by the MRC (Grant RG64071).