GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G protein-coupled receptors
| Autor: | Daniela Corda, Marilyn G. Farquhar, Bin Zheng, Christopher P. Berrie |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
G protein
Molecular Sequence Data phospholipid metabolism Receptors Cell Surface Biology Cell Line Substrate Specificity Mice Regulator of G protein signaling GTP-binding protein regulators GTP-Binding Proteins Catalytic Domain GDE domain Animals Humans Amino Acid Sequence Chromatography High Pressure Liquid G protein-coupled receptor Glycerophosphodiester phosphodiesterase Multidisciplinary Sequence Homology Amino Acid Phosphoric Diester Hydrolases Phosphodiesterase Biological Sciences phosphoinositide Cell biology RGS proteins Biochemistry Membrane topology Mutagenesis Site-Directed Signal transduction |
| Zdroj: | Zheng, Bin; Berrie, Christopher P; Corda, Daniela; & Farquhar, Marilyn G. (2003). GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G protein-coupled receptors. Proceedings of the National Academy of Sciences of the United States of America, 100(4), 1745-1750. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/5pf289pw |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0337605100 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|