Sphingolipids Function as Downstream Effectors of a Fungal PAQR
- 9 December 2008
- journal article
- research article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Molecular Pharmacology
- Vol. 75 (4), 866-875
- https://doi.org/10.1124/mol.108.049809
Abstract
The Izh2p protein from Saccharomyces cerevisiae belongs to the newly characterized progestin and adipoQ receptor (PAQR) superfamily of receptors whose mechanism of signal transduction is still unknown. Izh2p functions as a receptor for the plant PR-5 defensin osmotin and has pleiotropic effects on cellular biochemistry. One example of this pleiotropy is the Izh2p-dependent repression of FET3, a gene involved in iron-uptake. Although the physiological purpose of FET3 repression by Izh2p is a matter of speculation, it provides a reporter with which to probe the mechanism of signal transduction by this novel class of receptor. Receptors in the PAQR family share sequence similarity with enzymes involved in ceramide metabolism, which led to the hypothesis that sphingolipids are involved in Izh2p-dependent signaling. In this study, we demonstrate that drugs affecting sphingolipid metabolism, such as d-erythro-MAPP and myriocin, inhibit the effect of Izh2p on FET3. We also show that Izh2p causes an increase in steady-state levels of sphingoid base. Moreover, we show that Izh2p-independent increases in sphingoid bases recapitulate the effect of Izh2p on FET3. Finally, our data indicate that the Pkh1p and Pkh2p sphingoid base-sensing kinases are essential components of the Izh2p-dependent signaling pathway. In conclusion, our data indicate that Izh2p produces sphingoid bases and that these bioactive lipids probably function as the second messenger responsible for the effect of Izh2p on FET3.This publication has 40 references indexed in Scilit:
- Heterologous expression of human mPRα, mPRβ and mPRγ in yeast confirms their ability to function as membrane progesterone receptorsSteroids, 2008
- Novel analogs of d-e-MAPP and B13. Part 1: Synthesis and evaluation as potential anticancer agentsBioorganic & Medicinal Chemistry, 2008
- Globular adiponectin induces adhesion molecule expression through the sphingosine kinase pathway in vascular endothelial cellsLife Sciences, 2007
- Probing the mechanism of FET3 repression by Izh2p overexpressionBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2007
- Yeast sphingolipids: Recent developments in understanding biosynthesis, regulation, and functionBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2007
- Cyclic AMP-Dependent Protein Kinase Regulates the Subcellular Localization of Snf1-Sip1 Protein KinaseMolecular and Cellular Biology, 2004
- Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometryNature, 2002
- Preparation and Analysis of the Common Urinary Forms of Human Chorionic GonadotropinMethods, 2000
- BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequencesFEMS Microbiology Letters, 1999
- A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATIONCanadian Journal of Biochemistry and Physiology, 1959