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Published online 12 July 2004. doi:10.1083/jcb.200404150
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 2, 205-211
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Article

A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast



Prasenjit Mitra1, Yingjie Zhang1, Lucia E. Rameh4, Maria P. Ivshina1, Dannel McCollum2, John J. Nunnari3, Gregory M. Hendricks3, Monica L. Kerr5, Seth J. Field5, Lewis C. Cantley5, and Alonzo H. Ross1

1 Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655
2 Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655
3 Core Electron Microscopy Facility, University of Massachusetts Medical School, Worcester, MA 01655
4 Boston Biomedical Research Institute, Watertown, MA 02472
5 Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Hospital, Boston, MA 02115

Address correspondence to Alonzo H. Ross, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St., Rm. 819, Worcester, MA 01605. Tel.: (508) 856-8016. Fax: (508) 856-8017. email: Alonzo.Ross{at}umassmed.edu

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.

Key Words: PTEN; phosphatidylinositol kinase; phosphatidylinositol-3,4,5-trisphosphate; phosphatidylinositol-3-phosphatase; fission yeast

Abbreviations used in this paper: EMM, Edinburgh minimal medium; PI, phosphatidylinositol; PI(3,4,5)P3, PI-3,4,5-trisphosphate; PIP 5-kinase, PI-4-phosphate 5-kinase; PTEN, phosphatase and tensin homologue deleted on chromosome 10; ptn1{Delta}, ptn1 disrupted.


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