GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G protein-coupled receptors
- 7 February 2003
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 100 (4), 1745-1750
- https://doi.org/10.1073/pnas.0337605100
Abstract
Previously we identified MIR16 (membrane interacting protein of RGS16) as an integral membrane glycoprotein that interacts with regulator of G protein signaling proteins and shares significant sequence homology with bacterial glycerophosphodiester phosphodiesterases (GDEs), suggesting that it is a putative mammalian GDE. Here we show that MIR16 belongs to a large, evolutionarily conserved family of GDEs with a characteristic putative catalytic domain that shares a common motif (amino acids 92–116) with the catalytic domains of mammalian phosphoinositide phospholipases C. Expression of wild-type MIR16 (renamed GDE1), but not two catalytic domain mutants (E97A/D99A and H112A), leads to a dramatic increase in glycerophosphoinositol phosphodiesterase (GPI-PDE) activity in HEK 293T cells. Analysis of substrate specificity shows that GDE1/MIR16 selectively hydrolyzes GPI over glycerophosphocholine. The GPI-PDE activity of GDE1/MIR16 expressed in HEK 293T cells can be regulated by stimulation of G protein-coupled, α/β-adrenergic, and lysophospholipid receptors. Membrane topology studies suggest a model in which the catalytic GDE domain faces the lumen/extracellular space and the C terminus faces the cytoplasm. Our results suggest that by serving as a PDE for GPI with its activity regulated by G protein signaling, GDE1/MIR16 provides a link between phosphoinositide metabolism and G protein signal transduction.Keywords
This publication has 41 references indexed in Scilit:
- Reorganization of Actin Cytoskeleton by the Phosphoinositide Metabolite Glycerophosphoinositol 4-PhosphateMolecular Biology of the Cell, 2003
- Cellular Regulation of RGS Proteins: Modulators and Integrators of G Protein SignalingPublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2002
- Mechanisms of Regulation of Phospholipase D1 and D2 by the Heterotrimeric G Proteins G13 and GqPublished by Elsevier BV ,2002
- RGS-PX1, a GAP for Gα s and Sorting Nexin in Vesicular TraffickingScience, 2001
- The Regulator of G Protein Signaling FamilyAnnual Review of Pharmacology and Toxicology, 2000
- Mammalian lysophospholipasesBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1999
- REGULATION AND INHIBITION OF PHOSPHOLIPASE A2Annual Review of Pharmacology and Toxicology, 1999
- Catalytic Domain of Phosphoinositide-specific Phospholipase C (PLC)Journal of Biological Chemistry, 1998
- Phosphoinositide-Specific Phospholipase C δ1 Activity toward Micellar Substrates, Inositol 1,2-Cyclic Phosphate, and Other Water-Soluble Substrates: A Sequential Mechanism and Allosteric ActivationBiochemistry, 1997
- Rat kidney glycerylphosphorylcholine diesteraseBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1968