Authors
Mitra, PrasenjitZhang, Yingjie
Rameh, Lucia E.
Ivshina, Mariya P.
McCollum, Dannel
Nunnari, John J.
Hendricks, Gregory M.
Kerr, Monica L.
Field, Seth J.
Cantley, Lewis C.
Ross, Alonzo H.
UMass Chan Affiliations
Department of Cell BiologyMolecular Genetics and Microbiology
Department of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2004-07-14Keywords
1-Phosphatidylinositol 3-KinaseEvolution, Molecular
Mutation
Phosphatidylinositol Phosphates
Phosphoric Monoester Hydrolases
Phosphotransferases (Alcohol Group Acceptor)
Saccharomyces cerevisiae Proteins
Schizosaccharomyces
*Schizosaccharomyces pombe Proteins
Biochemistry
Biochemistry, Biophysics, and Structural Biology
Cell Biology
Microbiology
Molecular Genetics
Pharmacy and Pharmaceutical Sciences
Metadata
Show full item recordAbstract
The 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.Source
J Cell Biol. 2004 Jul 19;166(2):205-11. Epub 2004 Jul 12. Link to article on publisher's siteDOI
10.1083/jcb.200404150Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42580PubMed ID
15249580Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1083/jcb.200404150