Shank2 associates with and regulates Na+/H+ exchanger

Won Sun Han, Hwan Kim Kyung, Jae Jo Min, Hyun Lee Ji, Jinhee Yang, R. Brian Doctor, Orson W. Moe, Jinu Lee, Eunjoon Kim, Goo Lee Min

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Na+/H+ exchanger 3 (NHE3) plays a pivotal role in transepithelial Na+ and HCO3- absorption across a wide range of epithelia in the digestive and renal-genitourinary systems. Accumulating evidence suggests that PDZ-based adaptor proteins play an important role in regulating the trafficking and activity of NHE3. A search for NHE3-binding modular proteins using yeast two-hybrid assays led us to the PDZ-based adaptor Shank2. The interaction between Shank2 and NHE3 was further confirmed by immunoprecipitation and surface plasmon resonance studies. When expressed in PS120/ NHE3 cells, Shank2 increased the membrane expression and basal activity of NHE3 and attenuated the cAMP-dependent inhibition of NHE3 activity. Furthermore, knock-down of native Shank2 expression in Caco-2 epithelial cells by RNA interference decreased NHE3 protein expression as well as activity but amplified the inhibitory effect of cAMP on NHE3. These results indicate that Shank2 is a novel NHE3 interacting protein that is involved in the fine regulation of transepithelial salt and water transport through affecting NHE3 expression and activity.

Original languageEnglish
Pages (from-to)1461-1469
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number3
DOIs
Publication statusPublished - 2006 Jan 20

Fingerprint

Sodium-Hydrogen Antiporter
Urogenital System
Two-Hybrid System Techniques
Proteins
Fungal Proteins
Caco-2 Cells
Surface Plasmon Resonance
Surface plasmon resonance
RNA Interference
Immunoprecipitation
Assays
Carrier Proteins
Epithelium
Salts
Epithelial Cells
RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Han, W. S., Kyung, H. K., Min, J. J., Ji, H. L., Yang, J., Doctor, R. B., ... Min, G. L. (2006). Shank2 associates with and regulates Na+/H+ exchanger. Journal of Biological Chemistry, 281(3), 1461-1469. https://doi.org/10.1074/jbc.M509786200
Han, Won Sun ; Kyung, Hwan Kim ; Min, Jae Jo ; Ji, Hyun Lee ; Yang, Jinhee ; Doctor, R. Brian ; Moe, Orson W. ; Lee, Jinu ; Kim, Eunjoon ; Min, Goo Lee. / Shank2 associates with and regulates Na+/H+ exchanger. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 3. pp. 1461-1469.
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Han, WS, Kyung, HK, Min, JJ, Ji, HL, Yang, J, Doctor, RB, Moe, OW, Lee, J, Kim, E & Min, GL 2006, 'Shank2 associates with and regulates Na+/H+ exchanger', Journal of Biological Chemistry, vol. 281, no. 3, pp. 1461-1469. https://doi.org/10.1074/jbc.M509786200

Shank2 associates with and regulates Na+/H+ exchanger. / Han, Won Sun; Kyung, Hwan Kim; Min, Jae Jo; Ji, Hyun Lee; Yang, Jinhee; Doctor, R. Brian; Moe, Orson W.; Lee, Jinu; Kim, Eunjoon; Min, Goo Lee.

In: Journal of Biological Chemistry, Vol. 281, No. 3, 20.01.2006, p. 1461-1469.

Research output: Contribution to journalArticle

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Han WS, Kyung HK, Min JJ, Ji HL, Yang J, Doctor RB et al. Shank2 associates with and regulates Na+/H+ exchanger. Journal of Biological Chemistry. 2006 Jan 20;281(3):1461-1469. https://doi.org/10.1074/jbc.M509786200