Shank2 associates with and regulates Na+/H+ exchanger

WonSun 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

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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 (US)
Pages (from-to)1461-1469
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number3
DOIs
StatePublished - Jan 20 2006

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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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Han, W., 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

Shank2 associates with and regulates Na+/H+ exchanger. / Han, WonSun; 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

Han, W, 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
Han W, 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
Han, WonSun ; 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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