Signalling through phosphoinositide 3-kinases: the lipids take centre stage.
Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids at the 3' position of the inositol ring to generate the 3-phosphoinositides PI(3)P, PI(3,4) P2 and PI(3,4,5) P3. Recent research has shown that one way in which these lipids function in signal transduction and membrane trafficking is by interacting with 3-phosphoinositide-binding modules in a broad variety of proteins. Specifically, certain FYVE domains bind PI(3)P whereas certain pleckstrin homology domains bind PI(3,4) P2 and/or PI(3,4,5) P3. Also in 1998, PTEN - a major tumour suppressor in human cancer - was also shown to antagonise PI3K signalling by removing the 3-phosphate from 3-phosphoinositides.
Leevers
S J
SJ
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK. sallyl@ludwig.ucl.ac.uk
Vanhaesebroeck
B
B
Waterfield
M D
MD
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D008563:Membrane Lipids / Q000502:physiology*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010716:Phosphatidylinositols / Q000502:physiology*; D010750:Phosphoproteins; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000145:classification / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D001798:Blood Proteins; D007527:Isoenzymes; D008563:Membrane Lipids; D009363:Neoplasm Proteins; D010716:Phosphatidylinositols; D010750:Phosphoproteins; D025521:Tumor Suppressor Proteins; C039077:platelet protein P47; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D019204:GTP-Binding Proteins