[PMID]: | 28381458 |
[Au] Autor: | Cheung PW; Ueberdiek L; Day J; Bouley R; Brown D |
[Ad] Endereço: | Center for Systems Biology, Program in Membrane Biology and Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. |
[Ti] Título: | Protein phosphatase 2C is responsible for VP-induced dephosphorylation of AQP2 serine 261. |
[So] Source: | Am J Physiol Renal Physiol;313(2):F404-F413, 2017 Aug 01. |
[Is] ISSN: | 1522-1466 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Aquaporin 2 (AQP2) trafficking is regulated by phosphorylation and dephosphorylation of serine residues in the AQP2 COOH terminus. Vasopressin (VP) binding to its receptor (V2R) leads to a cascade of events that result in phosphorylation of serine 256 (S256), S264, and S269, but dephosphorylation of S261. To identify which phosphatase is responsible for VP-induced S261 dephosphorylation, we pretreated cells with different phosphatase inhibitors before VP stimulation. Sanguinarine, a specific protein phosphatase (PP) 2C inhibitor, but not inhibitors of PP1, PP2A (okadaic acid), or PP2B (cyclosporine), abolished VP-induced S261 dephosphorylation. However, sanguinarine and VP significantly increased phosphorylation of ERK, a kinase that can phosphorylate S261; inhibition of ERK by PD98059 partially decreased baseline S261 phosphorylation. These data support a role of ERK in S261 phosphorylation but suggest that, upon VP treatment, increased phosphatase activity overcomes the increase in ERK activity, resulting in overall dephosphorylation of S261. We also found that sanguinarine abolished VP-induced S261 dephosphorylation in cells expressing mutated AQP2 S256A, suggesting that the phosphorylation state of S261 is independent of S256. Sanguinarine alone did not induce AQP2 membrane trafficking, nor did it inhibit VP-induced AQP2 membrane accumulation in cells and kidney tissues, suggesting that S261 does not play an observable role in acute AQP2 membrane accumulation. In conclusion, PP2C activity is required for S261 AQP2 dephosphorylation upon VP stimulation, which occurs independently of S256 phosphorylation. Understanding the pathways involved in modulating PP2C will help elucidate the role of S261 in cellular events involving AQP2. |
[Mh] Termos MeSH primário: |
Aquaporina 2/metabolismo Rim/efeitos dos fármacos Vasopressinas/farmacologia
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[Mh] Termos MeSH secundário: |
Animais Aquaporina 2/genética Inibidores Enzimáticos/farmacologia MAP Quinases Reguladas por Sinal Extracelular/metabolismo Técnicas In Vitro Rim/enzimologia Células LLC-PK1 Mutação Fosforilação Proteína Fosfatase 2C/antagonistas & inibidores Proteína Fosfatase 2C/metabolismo Transporte Proteico Ratos Sprague-Dawley Receptores de Vasopressinas/agonistas Receptores de Vasopressinas/metabolismo Serina Transdução de Sinais/efeitos dos fármacos Suínos Transfecção Vasopressinas/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Aqp2 protein, rat); 0 (Aquaporin 2); 0 (Enzyme Inhibitors); 0 (Receptors, Vasopressin); 0 (V2 vasopressin receptor, rat); 11000-17-2 (Vasopressins); 452VLY9402 (Serine); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 3.1.3.16 (Protein Phosphatase 2C) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 171020 |
[Lr] Data última revisão:
| 171020 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170407 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1152/ajprenal.00004.2017 |
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