Department of Biochemistry and Molecular Pharmacology; Molecular Genetics and Microbiology; Department of Cell Biology
1-Phosphatidylinositol 3-Kinase; Evolution, 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
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.
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Citation: J Cell Biol. 2004 Jul 19;166(2):205-11. Epub 2004 Jul 12. Link to article on publisher's site
DOI of Published Version
The Journal of cell biology
Mitra, Prasenjit; Zhang, Yingjie; Rameh, Lucia E.; Ivshina, Mariya P.; McCollum, Dannel; Nunnari, John J.; Hendricks, Gregory M.; Kerr, Monica L.; Field, Seth J.; Cantley, Lewis C.; and Ross, Alonzo H., "A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast" (2004). Open Access Articles. 915.