Mitra, PrasenjitZhang, YingjieRameh, Lucia E.Ivshina, Mariya P.McCollum, DannelNunnari, John J.Hendricks, Gregory M.Kerr, Monica L.Field, Seth J.Cantley, Lewis C.Ross, Alonzo H.2022-08-232022-08-232004-07-142008-08-15J Cell Biol. 2004 Jul 19;166(2):205-11. Epub 2004 Jul 12. <a href="http://dx.doi.org/10.1083/jcb.200404150">Link to article on publisher's site</a>0021-9525 (Print)10.1083/jcb.20040415015249580https://hdl.handle.net/20.500.14038/42580The mammalian tumor suppressor, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), inhibits cell growth and survival by dephosphorylating phosphatidylinositol-(3,4,5)-trisphosphate (PI[3,4,5]P3). We have found a homologue of PTEN in the fission yeast, Schizosaccharomyces pombe (ptn1). This was an unexpected finding because yeast (S. pombe and Saccharomyces cerevisiae) lack the class I phosphoinositide 3-kinases that generate PI(3,4,5)P3 in higher eukaryotes. Indeed, PI(3,4,5)P3 has not been detected in yeast. Surprisingly, upon deletion of ptn1 in S. pombe, PI(3,4,5)P3 became detectable at levels comparable to those in mammalian cells, indicating that a pathway exists for synthesis of this lipid and that the S. pombe ptn1, like mammalian PTEN, suppresses PI(3,4,5)P3 levels. By examining various mutants, we show that synthesis of PI(3,4,5)P3 in S. pombe requires the class III phosphoinositide 3-kinase, vps34p, and the phosphatidylinositol-4-phosphate 5-kinase, its3p, but does not require the phosphatidylinositol-3-phosphate 5-kinase, fab1p. These studies suggest that a pathway for PI(3,4,5)P3 synthesis downstream of a class III phosphoinositide 3-kinase evolved before the appearance of class I phosphoinositide 3-kinases.en-US1-Phosphatidylinositol 3-KinaseEvolution, MolecularMutationPhosphatidylinositol PhosphatesPhosphoric Monoester HydrolasesPhosphotransferases (Alcohol Group Acceptor)Saccharomyces cerevisiae ProteinsSchizosaccharomyces*Schizosaccharomyces pombe ProteinsBiochemistryBiochemistry, Biophysics, and Structural BiologyCell BiologyMicrobiologyMolecular GeneticsPharmacy and Pharmaceutical SciencesJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1914&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/915579804oapubs/915