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Protein Phosphatase 1 Inhibitor-1 Mediates the cAMP-Dependent Stimulation of the Renal NaCl Cotransporter

J Am Soc Nephrol. 2019; 
Penton D, Moser S, Wengi A, Czogalla J, Rosenbaek LL, Rigendinger F, Faresse N, Martins JR, Fenton RA, Loffing-Cueni D, Loffing J, .
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摘要

A number of cAMP-elevating hormones stimulate phosphorylation (and hence activity) of the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). Evidence suggests that protein phosphatase 1 (PP1) and other protein phosphatases modulate NCC phosphorylation, but little is known about PP1's role and the mechanism regulating its function in the DCT.,We used ex vivo mouse kidney preparations to test whether a DCT-enriched inhibitor of PP1, protein phosphatase 1 inhibitor-1 (I1), mediates cAMP's effects on NCC, and conducted yeast two-hybrid and coimmunoprecipitation experiments in NCC-expressing MDCK cells to explore protein interactions.,Treating isolated DCTs with forskolin and IBMX increased NCC phosphor... More

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