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Open Access Articles

Title

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

Authors

Prasenjit Mitra, University of Massachusetts Medical School
Yingjie Zhang, University of Massachusetts Medical School
Lucia E. Rameh
Mariya P. Ivshina, University of Massachusetts Medical School
Dannel McCollum, University of Massachusetts Medical School
John J. Nunnari
Gregory M. Hendricks, University of Massachusetts Medical School
Monica L. Kerr
Seth J. Field
Lewis C. Cantley
Alonzo H. Ross, University of Massachusetts Medical School

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Molecular Genetics and Microbiology; Department of Cell Biology

Date

July 2004

Document Type

Article

Subjects

1-Phosphatidylinositol 3-Kinase; Evolution, Molecular; Mutation; Phosphatidylinositol Phosphates; Phosphoric Monoester Hydrolases; Phosphotransferases (Alcohol Group Acceptor); Saccharomyces cerevisiae Proteins; Schizosaccharomyces; *Schizosaccharomyces pombe Proteins

Abstract

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.