In the brush border of intestinal and kidney epithelial cells, scaffolding proteins ezrin, Na+-H+ exchanger regulatory factor (NHERF)1 and NHERF2 play important roles in linking transmembrane proteins to the cytoskeleton and assembling signalling regulatory complexes. The last 30 carboxyl residues of NHERF1 and NHERF2 form the EBDs [ezrin, radixin and moesin (ERM)-binding domain]. The current study found that NHERF1/2 contain an ERM-binding regulatory sequence (EBRS), which facilitates the interaction between the EBD and ezrin. The EBRSs are located within 24 and 19 residues immediately upstream of EBDs for NHERF1 and NHERF2 respectively. In OK (opossum kidney) epithelial cells, EBRSs are necessary along with the EBD to distribute NHERF1 and NHERF2 exclusively to the apical domain. Furthermore, phosphorylation of Ser303 located in the EBRS of NHERF2, decreases the binding affinity for ezrin, dislocates apical NHERF2 into the cytosol and increases the NHERF2 microvillar mobility rate. Moreover, increased phosphorylation of Ser303 was functionally significant preventing acute stimulation of NHE3 (Na+-H+ exchanger 3) activity by dexamethasone.
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Research Article|
August 06 2015
The NHERF2 sequence adjacent and upstream of the ERM-binding domain affects NHERF2–ezrin binding and dexamethasone stimulated NHE3 activity
Jianbo Yang;
Jianbo Yang
1
*Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
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Rafiquel Sarker;
Rafiquel Sarker
1
*Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
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Varsha Singh;
Varsha Singh
*Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
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Prateeti Sarker;
Prateeti Sarker
*Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
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Jianyi Yin;
Jianyi Yin
*Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
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Tian-E Chen;
Tian-E Chen
*Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
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Raghothama Chaerkady;
Raghothama Chaerkady
†Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
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Xuhang Li;
Xuhang Li
*Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
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C. Ming Tse;
C. Ming Tse
*Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
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Mark Donowitz
Mark Donowitz
2
*Departments of Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
‡Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, U.S.A.
2To whom correspondence should be addressed (email mdonowit@jhmi.edu).
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Publisher: Portland Press Ltd
Received:
February 20 2015
Revision Received:
May 26 2015
Accepted:
June 16 2015
Accepted Manuscript online:
June 16 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2015 Authors; published by Portland Press Limited
2015
Biochem J (2015) 470 (1): 77–90.
Article history
Received:
February 20 2015
Revision Received:
May 26 2015
Accepted:
June 16 2015
Accepted Manuscript online:
June 16 2015
Citation
Jianbo Yang, Rafiquel Sarker, Varsha Singh, Prateeti Sarker, Jianyi Yin, Tian-E Chen, Raghothama Chaerkady, Xuhang Li, C. Ming Tse, Mark Donowitz; The NHERF2 sequence adjacent and upstream of the ERM-binding domain affects NHERF2–ezrin binding and dexamethasone stimulated NHE3 activity. Biochem J 15 August 2015; 470 (1): 77–90. doi: https://doi.org/10.1042/BJ20150238
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