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PP2R2C is involved in the resensitization of the dopamine D1 receptor in human renal proximal tubule cells.
Author(s) -
Zhang Yanrong,
Yang Yu,
Villar Van Anthony,
Pascua Annabelle,
Armando Ines,
Jose Pedro A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.818.1
Subject(s) - protein phosphatase 2 , fenoldopam , protein subunit , microbiology and biotechnology , pronephros , dephosphorylation , receptor , phosphorylation , phosphatase , chemistry , distal convoluted tubule , immunoprecipitation , medicine , endocrinology , dopamine , biology , dopamine receptor , kidney , biochemistry , reabsorption , xenopus , gene
Dopamine is important in the regulation of blood pressure, sodium balance, and renal function acting through D1‐like and D2‐like dopamine receptors. Protein phosphatase 2A (PP2A) is a heterotrimeric serine/threonine phosphatase. There is tissue specific expression of the B subunits of PP2A; human renal proximal tubule cells express B55γ (PP2R2C, γ isoform, B regulatory subunit) and PP2A B56 γ (□ isoform, B′ regulatory subunit). We have reported that dopamine D1 receptor (D 1 R) dephosphorylation, recycling to the cell surface membrane, and resensitization are dependent on PP2A activity (Kidney Int. 2006;70:1072–9). We aimed to determine the role of PP2R2C in the spatial and temporal events involved in the resensitization of D 1 R in human renal proximal tubule cells. PP2A B (entire B regulatory subunit), PP2A C (catalytic subunit) and PP2R2C subunits were found to be expressed in the cytosol of immortalized human renal proximal tubular cells by confocal microscopy (n=3). Co‐immunoprecipitation studies demonstrated that the D 1 R interacts with PP2A B, PP2A C and PP2R2C subunits (n=3). Treatment with the D1‐like agonist fenoldopam (FEN, 1 □M) decreased expression of PP2A B (15%; n=3) and PP2A B56γ (30%; n=3) but increased that of PP2R2C (25%: n=3). Treatment with FEN for 15 min increased total phosphatase activity (18%; n=2). Upon FEN stimulation the D 1 R internalized and co‐localized with of PP2R2C (n=3). These results suggest that PP2A and PP2R2C are involved in the regulation of the resensitization and trafficking of the D 1 R. This work was supported in part by grants from the National Institutes of Health, HL68686, HL23081, HL074940, HL092196 and DK39308