Phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ), a lipid signalling enigma

Adv Biol Regul. 2016 May:61:47-50. doi: 10.1016/j.jbior.2015.11.007. Epub 2015 Dec 2.

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.

Keywords: PI5P; PI5P4K; PI5P4Kγ; Phosphatidylinositol 5-phosphate; Phosphatidylinositol 5-phosphate 4-kinase γ.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Binding Sites
  • Binding, Competitive
  • Catechols / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Protein Binding
  • Signal Transduction*
  • Tyrphostins / pharmacology*

Substances

  • AG 538
  • Catechols
  • Enzyme Inhibitors
  • Isoenzymes
  • Phosphatidylinositol Phosphates
  • Tyrphostins
  • phosphatidylinositol 5-phosphate
  • Adenosine Triphosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-phosphatidylinositol-4-phosphate 5-kinase