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

47 Scopus citations


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
Issue number3
StatePublished - Jan 20 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Han, W., Kyung, H. K., Min, J. J., Ji, H. L., Yang, J., Doctor, R. B., Moe, O. W., Lee, J., Kim, E., & Min, G. L. (2006). Shank2 associates with and regulates Na+/H+ exchanger. Journal of Biological Chemistry, 281(3), 1461-1469.