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 De Paoli-Roach, Robert J. Lefkowitz

Research output: Contribution to journalArticle

150 Citations (Scopus)

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
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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Protein Phosphatase 2
G-Protein-Coupled Receptors
Substrate Specificity
Phosphoric Monoester Hydrolases
G-Protein-Coupled Receptor Kinases
Okadaic Acid
Protamines
Detergents
Gel Chromatography
Membrane Proteins
Western Blotting
Phosphorylation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The G-protein-coupled receptor phosphatase : A protein phosphatase type 2A with a distinct subcellular distribution and substrate specificity. / Pitcher, Julie A.; Payne, E. Sturgis; Csortos, Csilla; De Paoli-Roach, Anna; Lefkowitz, Robert J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 18, 29.08.1995, p. 8343-8347.

Research output: Contribution to journalArticle

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