Skip to main content
SpringerLink
Log in

NHERF

  • Reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

  • 38 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anzai N, Miyazaki H, Noshiro R, Khamdang S, Chairoungdua A, Shin HJ, et al. The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus. J Biol Chem. 2004;279(44):45942–50.

    Article  CAS  PubMed  Google Scholar 

  • Breton S, Wiederhold T, Marshansky V, Nsumu NN, Ramesh V, Brown D. The B1 subunit of the H+ATPase is a PDZ domain-binding protein. Colocalization with NHE-RF in renal B-intercalated cells. J Biol Chem. 2000;275(24):18219–24.

    Article  CAS  PubMed  Google Scholar 

  • Cha B, Kim JH, Hut H, Hogema BM, Nadarja J, Zizak M, et al. cGMP inhibition of Na+/H+ antiporter 3 (NHE3) requires PDZ domain adapter NHERF2, a broad specificity protein kinase G-anchoring protein. J Biol Chem. 2005;280(17):16642–50.

    Article  CAS  PubMed  Google Scholar 

  • Donowitz M, Cha B, Zachos NC, Brett CL, Sharma A, Tse CM, et al. NHERF family and NHE3 regulation. J Physiol. 2005;567(Pt 1):3–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Embark HM, Setiawan I, Poppendieck S, van de Graaf SF, Boehmer C, Palmada M, et al. Regulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3 expressed in Xenopus oocytes. Cell Physiol Biochem. 2004;14(4–6):203–12.

    Article  CAS  PubMed  Google Scholar 

  • Georgescu MM, Morales FC, Molina JR, Hayashi Y. Roles of NHERF1/EBP50 in cancer. Curr Mol Med. 2008;8(6):459–68.

    Article  CAS  PubMed  Google Scholar 

  • Gisler SM, Stagljar I, Traebert M, Bacic D, Biber J, Murer H. Interaction of the type IIa Na/Pi cotransporter with PDZ proteins. J Biol Chem. 2001;276(12):9206–13.

    Article  CAS  PubMed  Google Scholar 

  • Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, et al. PDZK1: I. a major scaffolder in brush borders of proximal tubular cells. Kidney Int. 2003;64(5):1733–45.

    Article  CAS  PubMed  Google Scholar 

  • Hall RA, Premont RT, Chow CW, Blitzer JT, Pitcher JA, Claing A, et al. The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. Nature. 1998;392(6676):626–30.

    Article  CAS  PubMed  Google Scholar 

  • Hall RA, Spurney RF, Premont RT, Rahman N, Blitzer JT, Pitcher JA, et al. G protein-coupled receptor kinase 6A phosphorylates the Na(+)/H(+) exchanger regulatory factor via a PDZ domain-mediated interaction. J Biol Chem. 1999;274(34):24328–34.

    Article  CAS  PubMed  Google Scholar 

  • He P, Yun CC. Mechanisms of the regulation of the intestinal Na+/H+ exchanger NHE3. J Biomed Biotechnol. 2010:238080.

    Google Scholar 

  • Hildreth KL, Wu JH, Barak LS, Exum ST, Kim LK, Peppel K, et al. Phosphorylation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-2 reduces receptor signaling and interaction with the Na(+)/H(+) exchanger regulatory factor. J Biol Chem. 2004;279(40):41775–82.

    Article  CAS  PubMed  Google Scholar 

  • Hwang JI, Heo K, Shin KJ, Kim E, Yun C, Ryu SH, et al. Regulation of phospholipase C-beta 3 activity by Na+/H+ exchanger regulatory factor 2. J Biol Chem. 2000;275(22):16632–7.

    Article  CAS  PubMed  Google Scholar 

  • Joubert L, Hanson B, Barthet G, Sebben M, Claeysen S, Hong W, et al. New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a receptor splice variant: roles in receptor targeting. J Cell Sci. 2004;117(Pt 22):5367–79.

    Article  CAS  PubMed  Google Scholar 

  • Kato Y, Yoshida K, Watanabe C, Sai Y, Tsuji A. Screening of the interaction between xenobiotic transporters and PDZ proteins. Pharm Res. 2004;21(10):1886–94.

    Article  CAS  PubMed  Google Scholar 

  • Kato Y, Sai Y, Yoshida K, Watanabe C, Hirata T, Tsuji A. PDZK1 directly regulates the function of organic cation/carnitine transporter OCTN2. Mol Pharmacol. 2005;67(3):734–43.

    Article  CAS  PubMed  Google Scholar 

  • Kim HJ, Yang DK, So I. PDZ domain-containing protein as a physiological modulator of TRPV6. Biochem Biophys Res Commun. 2007;361(2):433–8.

    Article  CAS  PubMed  Google Scholar 

  • Lamprecht G, Weinman EJ, Yun CH. The role of NHERF and E3KARP in the cAMP-mediated inhibition of NHE3. J Biol Chem. 1998;273(45):29972–8.

    Article  CAS  PubMed  Google Scholar 

  • Lazar CS, Cresson CM, Lauffenburger DA, Gill GN. The Na+/H+ exchanger regulatory factor stabilizes epidermal growth factor receptors at the cell surface. Mol Biol Cell. 2004;15(12):5470–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee-Kwon W, Kim JH, Choi JW, Kawano K, Cha B, Dartt DA, et al. Ca2+-dependent inhibition of NHE3 requires PKC alpha which binds to E3KARP to decrease surface NHE3 containing plasma membrane complexes. Am J Physiol Cell Physiol. 2003;285(6):C1527–36.

    Article  CAS  PubMed  Google Scholar 

  • Li JG, Chen CG, Liu-Chen LY. Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate. J Biol Chem. 2002;277(30):27545–52.

    Article  CAS  PubMed  Google Scholar 

  • Lin S, Yeruva S, He P, Singh AK, Zhang H, Chen M, et al. Lysophosphatidic acid stimulates the intestinal brush border Na(+)/H(+) exchanger 3 and fluid absorption via LPA(5) and NHERF2. Gastroenterology. 2010;138(2):649–58.

    Article  CAS  PubMed  Google Scholar 

  • Mahon MJ, Donowitz M, Yun CC, Segre GV. Na(+)/H(+) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. Nature. 2002;417(6891):858–61.

    Article  CAS  PubMed  Google Scholar 

  • Maudsley S, Zamah AM, Rahman N, Blitzer JT, Luttrell LM, Lefkowitz RJ, et al. Platelet-derived growth factor receptor association with Na(+)/H(+) exchanger regulatory factor potentiates receptor activity. Mol Cell Biol. 2000;20(22):8352–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mohler PJ, Kreda SM, Boucher RC, Sudol M, Stutts MJ, Milgram SL. Yes-associated protein 65 localizes p62(c-Yes) to the apical compartment of airway epithelia by association with EBP50. J Cell Biol. 1999;147(4):879–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Murthy A, Gonzalez-Agosti C, Cordero E, Pinney D, Candia C, Solomon F, et al. NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins. J Biol Chem. 1998;273(3):1273–6.

    Article  CAS  PubMed  Google Scholar 

  • Oh YS, Jo NW, Choi JW, Kim HS, Seo SW, Kang KO, et al. NHERF2 specifically interacts with LPA2 receptor and defines the specificity and efficiency of receptor-mediated phospholipase C-beta3 activation. Mol Cell Biol. 2004;24(11):5069–79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ritter SL, Hall RA. Fine-tuning of GPCR activity by receptor-interacting proteins. Nat Rev Mol Cell Biol. 2009;10(12):819–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Scott RO, Thelin WR, Milgram SL. A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor. J Biol Chem. 2002;277(25):22934–41.

    Article  CAS  PubMed  Google Scholar 

  • Shibata T, Chuma M, Kokubu A, Sakamoto M, Hirohashi S. EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma. Hepatology. 2003;38(1):178–86.

    Article  CAS  PubMed  Google Scholar 

  • Short DB, Trotter KW, Reczek D, Kreda SM, Bretscher A, Boucher RC, et al. An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton. J Biol Chem. 1998;273(31):19797–801.

    Article  CAS  PubMed  Google Scholar 

  • Singh AK, Riederer B, Krabbenhoft A, Rausch B, Bonhagen J, Lehmann U, et al. Differential roles of NHERF1, NHERF2, and PDZK1 in regulating CFTR-mediated intestinal anion secretion in mice. J Clin Invest. 2009;119(3):540–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sneddon WB, Syme CA, Bisello A, Magyar CE, Rochdi MD, Parent JL, et al. Activation-independent parathyroid hormone receptor internalization is regulated by NHERF1 (EBP50). J Biol Chem. 2003;278(44):43787–96.

    Article  CAS  PubMed  Google Scholar 

  • Sugiura T, Kato Y, Wakayama T, Silver DL, Kubo Y, Iseki S, et al. PDZK1 regulates two intestinal solute carriers (Slc15a1 and Slc22a5) in mice. Drug Metab Dispos. 2008;36(6):1181–8.

    Article  CAS  PubMed  Google Scholar 

  • Sun F, Hug MJ, Lewarchik CM, Yun CH, Bradbury NA, Frizzell RA. E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in airway cells. J Biol Chem. 2000;275(38):29539–46.

    Article  CAS  PubMed  Google Scholar 

  • Tachibana K, Anzai N, Ueda C, Katayama T, Yamasaki D, Kirino T, et al. Regulation of the human PDZK1 expression by peroxisome proliferator-activated receptor alpha. FEBS Lett. 2008;582(28):3884–8.

    Article  CAS  PubMed  Google Scholar 

  • Takahashi Y, Morales FC, Kreimann EL, Georgescu MM. PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling. EMBO J. 2006;25(4):910–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Takeda T, McQuistan T, Orlando RA, Farquhar MG. Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. J Clin Invest. 2001;108(2):289–301.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tang Y, Tang J, Chen Z, Trost C, Flockerzi V, Li M, et al. Association of mammalian trp4 and phospholipase C isozymes with a PDZ domain-containing protein, NHERF. J Biol Chem. 2000;275(48):37559–64.

    Article  CAS  PubMed  Google Scholar 

  • Theisen CS, Wahl 3rd JK, Johnson KR, Wheelock MJ. NHERF links the N-cadherin/catenin complex to the platelet-derived growth factor receptor to modulate the actin cytoskeleton and regulate cell motility. Mol Biol Cell. 2007;18(4):1220–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang S, Yue H, Derin RB, Guggino WB, Li M. Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity. Cell. 2000;103(1):169–79.

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Yang Y, Friedman PA. Na/H exchange regulatory factor 1, a novel AKT-associating protein, regulates extracellular signal-regulated kinase signaling through a B-Raf-mediated pathway. Mol Biol Cell. 2008;19(4):1637–45.

    Article  PubMed  PubMed Central  Google Scholar 

  • Watanabe C, Kato Y, Sugiura T, Kubo Y, Wakayama T, Iseki S, et al. PDZ adaptor protein PDZK2 stimulates transport activity of organic cation/carnitine transporter OCTN2 by modulating cell surface expression. Drug Metab Dispos. 2006;34(11):1927–34.

    Article  CAS  PubMed  Google Scholar 

  • Weinman EJ, Steplock D, Wang Y, Shenolikar S. Characterization of a protein cofactor that mediates protein kinase A regulation of the renal brush border membrane Na(+)-H+ exchanger. J Clin Invest. 1995;95(5):2143–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Weinman EJ, Cunningham R, Wade JB, Shenolikar S. The role of NHERF-1 in the regulation of renal proximal tubule sodium-hydrogen exchanger 3 and sodium-dependent phosphate cotransporter 2a. J Physiol. 2005;567(Pt 1):27–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Weinman EJ, Biswas RS, Peng G, Shen L, Turner CLEX, et al. Parathyroid hormone inhibits renal phosphate transport by phosphorylation of serine 77 of sodium-hydrogen exchanger regulatory factor-1. J Clin Invest. 2007;117(11):3412–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yun CHC, Oh S, Zizak M, Steplock D, Tsao S, Tse CM, et al. cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci USA. 1997;94(7):3010–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yun CC, Chen Y, Lang F. Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2. J Biol Chem. 2002;277(10):7676–83.

    Article  CAS  PubMed  Google Scholar 

  • Zachos NC, Hodson C, Kovbasnjuk O, Li X, Thelin WR, Cha B, et al. Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism. Cell Physiol Biochem. 2008;22(5–6):693–704.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by the grant from the National Institutes of Health (DK071597 and DK061418).

Author information

Authors and Affiliations

  1. Emory University School of Medicine, Division of Digestive Diseases, Department of Medicine, 1648 Pierce Drive, Atlanta, GA, 30322, USA

    Byong Kwon Yoo & C. Chris Yun

Authors
  1. Byong Kwon Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Chris Yun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Byong Kwon Yoo .

Editor information

Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Yoo, B.K., Chris Yun, C. (2018). NHERF. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_393

Download citation

Publish with us

Policies and ethics

Search

Navigation