The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Functional identification of protein phosphatase 1-binding consensus residues in NBCe1-B

  • Lee, Kyu Pil (Laboratory of Physiology, College of Veterinary Medicine, Chungnam National University) ;
  • Kim, Hyun Jin (Department of Physiology, School of Medicine, Sungkyunkwan University) ;
  • Yang, Dongki (Department of Physiology, College of Medicine, Gachon University)
  • Received : 2017.10.10
  • Accepted : 2017.11.19
  • Published : 2018.01.01
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Abstract

Protein phosphatase 1 (PP1) is involved in various signal transduction mechanisms as an extensive regulator. The PP1 catalytic subunit (PP1c) recognizes and binds to PP1-binding consensus residues (FxxR/KxR/K) in NBCe1-B. Consequently, we focused on identifying the function of the PP1-binding consensus residue, $^{922}FMDRLK^{927}$, in NBCe1-B. Using site-directed mutagenesis and co-immunoprecipitation assays, we revealed that in cases where the residues were substituted (F922A, R925A, and K927A) or deleted (deletion of amino acids 922-927), NBCe1-B mutants inhibited PP1 binding to NBCe1-B. Additionally, by recording the intracellular pH, we found that PP1-binding consensus residues in NBCe1-B were not only critical for NBCe1-B activity, but also relevant to its surface expression level. Therefore, we reported that NBCe1-B, as a substrate of PP1, contains these residues in the C-terminal region and that the direct interaction between NBCe1-B and PP1 is functionally critical in controlling the regulation of the ${HCO_3}^-$ transport. These results suggested that like IRBIT, PP1 was another novel regulator of ${HCO_3}^-$ secretion in several types of epithelia.

Keywords

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