The Korean Journal of Physiology and Pharmacology

  • 제20권4호
  • /
  • Pages.433-440
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  • 2016
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Ahcyl2 upregulates NBCe1-B via multiple serine residues of the PEST domain-mediated association

  • Park, Pil Whan (Department of Laboratory Medicine, Gachon University Gil Hospital) ;
  • Ahn, Jeong Yeal (Department of Laboratory Medicine, Gachon University Gil Hospital) ;
  • Yang, Dongki (Department of Physiology, College of Medicine, Gachon University)
  • 투고 : 2016.04.25
  • 심사 : 2016.05.31
  • 발행 : 2016.07.01
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초록

Inositol-1,4,5-triphosphate [$IP_3$] receptors binding protein released with $IP_3$ (IRBIT) was previously reported as an activator of NBCe1-B. Recent studies have characterized IRBIT homologue S-Adenosylhomocysteine hydrolase-like 2 (AHCYL2). AHCYL2 is highly homologous to IRBIT (88%) and heteromerizes with IRBIT. The two important domains in the N-terminus of AHCYL2 are a PEST domain and a coiled-coil domain which are highly comparable to those in IRBIT. Therefore, in this study, we tried to identify the role of those domains in mouse AHCYL2 (Ahcyl2), and we succeeded in identifying PEST domain of Ahcyl2 as a regulation region for NBCe1-B activity. Site directed mutagenesis and coimmunoprecipitation assay showed that NBCe1-B binds to the N-terminal Ahcyl2-PEST domain, and its binding is determined by the phosphorylation of 4 critical serine residues (Ser151, Ser154, Ser157, and Ser160) in Ahcyl2 PEST domain. Also we revealed that 4 critical serine residues in Ahcyl2 PEST domain are indispensable for the activation of NBCe1-B using measurement of intracellular pH experiment. Thus, these results suggested that the NBCe1-B is interacted with 4 critical serine residues in Ahcyl2 PEST domain, which play an important role in intracellular pH regulation through NBCe1-B.

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참고문헌

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  2. Expression of the B splice variant of NBCe1 (SLC4A4) in the mouse kidney vol.315, pp.3, 2018, https://doi.org/10.1152/ajprenal.00515.2017
  3. Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis vol.2020, pp.None, 2016, https://doi.org/10.1155/2020/4927547
  4. Both IRBIT and long-IRBIT bind to and coordinately regulate Cl−/HCO3− exchanger AE2 activity through modulating the lysosomal degradation of AE2 vol.11, pp.1, 2021, https://doi.org/10.1038/s41598-021-85499-6