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Expanding the role of NHERF, a PDZ-domain containing protein adapter, to growth regulation

Oncogene volume 20, pages 6309–6314 (2001)Cite this article

Abstract

NHERF (Na+/H+ exchanger regulatory factor or NHERF-1) and E3KARP (NHE3 kinase A regulatory protein or NHERF-2) are structurally related protein adapters that are highly expressed in epithelial tissues. NHERF proteins contain two tandem PDZ domains and a C-terminal sequence that binds several members of the ERM (ezrin-radixin-moesin) family of membrane-cytoskeletal adapters. Although identified as a regulator of NHE3, recent evidence points to a broadening role for NHERF in the function, localization and/or turnover of G-protein coupled receptors, platelet-derived growth factor receptor and ion transporters such as CFTR, Na/Pi cotransporter, Na/HCO3 cotransporter and Trp (calcium) channels. NHERF also recruits non-membrane proteins such as the c-Yes/YAP-65 complex, members of the phospholipase Cβ family and the GRK6A protein kinase to apical surface of polarized epithelial cells where they regulate or respond to membrane signals. While two distinct models have been proposed for NHERF's role in signal transduction, the common theme is NHERF's ability to bring together membrane and non-membrane proteins to regulate cell metabolism and growth. NHERF overexpression in human breast cancers and mutations in NHERF targets, such as CFTR and merlin, the product of Neurofibromatosis NF2 tumor suppressor gene, that impair NHERF binding suggest that aberrant NHERF function contributes to human disease.

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Acknowledgements

Studies on NHERF in the Weinman and Shenolikar laboratories are supported by grants from NIH DK55881 (to EJ Weinman and S Shenolikar) and Veterans Administration (to EJ Weinman). JW Voltz is supported by a predoctoral fellowship from the Department of Defense Breast Cancer Program (DAMD-17-98-1-8070).

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Authors and Affiliations

  1. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, North Carolina, USA

    James W Voltz & Shirish Shenolikar

  2. Department of Medicine, Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21202, Maryland, USA

    Edward J Weinman

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  1. James W Voltz
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Correspondence to Shirish Shenolikar.

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Voltz, J., Weinman, E. & Shenolikar, S. Expanding the role of NHERF, a PDZ-domain containing protein adapter, to growth regulation. Oncogene 20, 6309–6314 (2001). https://doi.org/10.1038/sj.onc.1204774

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