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

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48 Citations (Scopus)


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
Issue number3
Publication statusPublished - 2006 Jan 20

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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