The G-protein-coupled receptor phosphatase: A protein phosphatase type 2A with a distinct subcellular distribution and substrate specificity

Julie A. Pitcher, E. Sturgis Payne, Csilla Csortos, Anna A. Depaoli-Roach, Robert J. Lefkowitz

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Abstract

Phosphorylation of G-protein-coupled receptors plays an important role in regulating their function. In this study the G-protein-coupled receptor phosphatase (GRP) capable of dephosphorylating G-protein-coupled receptor kinase-phosphorylated receptors is described. The GRP activity of bovine brain is a latent oligomeric form of protein phosphatase type 2A (PP-2A) exclusively associated with the particulate fraction. GRP activity is observed only when assayed in the presence of protamine or when phosphatase- containing fractions are subjected to freeze/thaw treatment under reducing conditions. Consistent with its identification as a member of the PP-2A family, the GRP is potently inhibited by okadaic acid but not by 1-2, the specific inhibitor of protein phosphatase type 1. Solubilization of the membrane-associated GRP followed by gel filtration in the absence of detergent yields a 150-kDa peak of latent receptor phosphatase activity. Western blot analysis of this phosphatase reveals a likely subunit composition of AB(α)C. PP-2A of this subunit composition has previously been characterized as a soluble enzyme, yet negligible soluble GRP activity was observed. The subcellular distribution and substrate specificity of the GRP suggests significant differences between it and previously characterized forms of PP-2A.

Original languageEnglish (US)
Pages (from-to)8343-8347
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number18
DOIs
StatePublished - Aug 29 1995

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