Discoveries of the phosphatidate phosphatase genes in yeast published in the Journal of Biological Chemistry

George M Carman

doi:10.1074/jbc.tm118.004159

Abstract

This JBC Review on the discoveries of yeast phosphatidate (PA) phosphatase genes is dedicated to Dr. Herbert Tabor, Editor-in-Chief of the Journal of Biological Chemistry (JBC) for 40 years, on the occasion of his 100th birthday. Here, I reflect on the discoveries of the APP1, DPP1, LPP1, and PAH1 genes encoding all the PA phosphatase enzymes in yeast. PA phosphatase catalyzes PA dephosphorylation to generate diacylglycerol; both substrate and product are key intermediates in the synthesis of membrane phospholipids and triacylglycerol. App1 and Pah1 are peripheral membrane proteins catalyzing an Mg2+-dependent reaction governed by the DXDX(T/V) phosphatase motif. Dpp1 and Lpp1 are integral membrane proteins that catalyze an Mg2+-independent reaction governed by the KX 6RP-PSGH-SRX 5HX 3D phosphatase motif. Pah1 is PA-specific and is the only PA phosphatase responsible for lipid synthesis at the nuclear/endoplasmic reticulum membrane. App1, Dpp1, and Lpp1, respectively, are localized to cortical actin patches and the vacuole and Golgi membranes; they utilize several lipid phosphate substrates, including PA, lyso-PA, and diacylglycerol pyrophosphate. App1 is postulated to be involved in endocytosis, whereas Dpp1 and Lpp1 may be involved in lipid signaling. Pah1 is the yeast lipin homolog of mice and humans. A host of cellular defects and lipid-based diseases associated with loss or overexpression of PA phosphatase in yeast, mice, and humans, highlights its importance to cell physiology.

Highlights

This JBC Review on the discoveries of yeast phosphatidate (PA) phosphatase genes is dedicated to Dr Herbert Tabor, Editor-in-Chief of the Journal of Biological Chemistry (JBC) for 40 years, on the occasion of his 100th birthday
We constructed a mutant that lacks both the DPP1 and LPP1 genes; the analysis of PA phosphatase activity in the mutant indicated that other PA phosphatase genes exist in yeast, including the gene coding for the 91-kDa enzyme (Fig. 3A) [63, 67]
Because the name SMP2 has no meaning in a functional sense, we renamed the gene PAH1 for phosphatidic acid phosphohydrolase. (We could not use the acronym PAP for the PA phosphatase gene because it was already being used for the poly(A) polymerase gene.) A bioinformatics analysis of Pah1 indicated that the protein contains a conserved haloacid dehalogenase (HAD)–like domain with the DXDX(T/V) motif found in a superfamily of Mg2ϩ-dependent phosphatase enzymes with diverse substrate specificity (Fig. 2) [71, 72]

Summary

Introduction

This JBC Review on the discoveries of yeast phosphatidate (PA) phosphatase genes is dedicated to Dr Herbert Tabor, Editor-in-Chief of the Journal of Biological Chemistry (JBC) for 40 years, on the occasion of his 100th birthday. I reflect on the discoveries of the APP1, DPP1, LPP1, and PAH1 genes encoding all the PA phosphatase enzymes in yeast. We constructed a mutant that lacks both the DPP1 and LPP1 genes; the analysis of PA phosphatase activity in the mutant indicated that other PA phosphatase genes exist in yeast, including the gene coding for the 91-kDa enzyme (Fig. 3A) [63, 67].

Results

Conclusion