DOI: 10.1073/pnas.94.7.3010. cAMP-mediated inhibition of the epithelial brush border Na <sup>+</sup> /H <sup>+</sup> exchanger, NHE3, requires an associated regulatory protein

cAMP-mediated inhibition of the epithelial brush border Na + /H + exchanger, NHE3, requires an associated regulatory protein

10.1073/pnas.94.7.3010

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

NHE3 is the Na + /H + exchanger located on the intestinal and renal brush border membrane, where it functions in transepithelial Na + absorption. The brush border Na + absorptive process is acutely inhibited by activation of cAMP-dependent protein kinase, but the molecular mechanism of this inhibitory effect is poorly understood. We have identified two regulatory proteins, E3KARP and NHERF, that interact with NHE3 to enable cAMP to inhibit NHE3. The two regulatory proteins are structurally related, sharing ≈50% identity in amino acid sequences. It has been previously shown that when NHE3 is transfected into PS120 fibroblasts or Caco-2 cells, cAMP failed to inhibit NHE3 activity. Northern blot analysis showed that both PS120 and Caco-2 cells lacked the expression of both E3KARP and NHERF. In contrast, other cell lines in which cAMP inhibits NHE3, including OK, CHO, and LLC-PK 1 cells, expressed NHERF-related regulatory proteins. To determine their functions in cAMP-dependent inhibition of NHE3, E3KARP and NHERF were transfected into PS120/NHE3 fibroblasts. Transfection in PS120/NHE3 fibroblasts with either NHERF or E3KARP reconstituted cAMP-induced inhibition of NHE3, resulting in 25–30% inhibition in these cells.

Bibliography

Yun, C. H. C., Oh, S., Zizak, M., Steplock, D., Tsao, S., Tse, C.-M., Weinman, E. J., & Donowitz, M. (1997). cAMP-mediated inhibition of the epithelial brush border Na + /H + exchanger, NHE3, requires an associatedâregulatoryâprotein. Proceedings of the National Academy of Sciences, 94(7), 3010â3015.

Authors 8

C. H. Chris Yun (first)
Soohyuk Oh (additional)
Mirza Zizak (additional)
Deborah Steplock (additional)
Su Tsao (additional)
Chung-Ming Tse (additional)
Edward J. Weinman (additional)
Mark Donowitz (additional)

References 35 Referenced 351

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:29 p.m.)
Indexed	1 week ago (Aug. 23, 2025, 12:58 a.m.)
Issued	28 years, 4 months ago (April 1, 1997)
Published	28 years, 4 months ago (April 1, 1997)
Published Online	28 years, 4 months ago (April 1, 1997)
Published Print	28 years, 4 months ago (April 1, 1997)

Funders 0

None

BibTeX

@article{Yun_1997, title={cAMP-mediated inhibition of the epithelial brush border Na + /H + exchanger, NHE3, requires an associated regulatory protein}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.7.3010}, DOI={10.1073/pnas.94.7.3010}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Yun, C. H. Chris and Oh, Soohyuk and Zizak, Mirza and Steplock, Deborah and Tsao, Su and Tse, Chung-Ming and Weinman, Edward J. and Donowitz, Mark}, year={1997}, month=apr, pages={3010–3015} }

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  "abstract": "<jats:p>\n            NHE3 is the Na\n            <jats:sup>+</jats:sup>\n            /H\n            <jats:sup>+</jats:sup>\n            exchanger located on the intestinal and renal brush border membrane, where it functions in transepithelial Na\n            <jats:sup>+</jats:sup>\n            absorption. The brush border Na\n            <jats:sup>+</jats:sup>\n            absorptive process is acutely inhibited by activation of cAMP-dependent protein kinase, but the molecular mechanism of this inhibitory effect is poorly understood. We have identified two regulatory proteins, E3KARP and NHERF, that interact with NHE3 to enable cAMP to inhibit NHE3. The two regulatory proteins are structurally related, sharing \u224850% identity in amino acid sequences. It has been previously shown that when NHE3 is transfected into PS120 fibroblasts or Caco-2 cells, cAMP failed to inhibit NHE3 activity. Northern blot analysis showed that both PS120 and Caco-2 cells lacked the expression of both E3KARP and NHERF. In contrast, other cell lines in which cAMP inhibits NHE3, including OK, CHO, and LLC-PK\n            <jats:sub>1</jats:sub>\n            cells, expressed NHERF-related regulatory proteins. To determine their functions in cAMP-dependent inhibition of NHE3, E3KARP and NHERF were transfected into PS120/NHE3 fibroblasts. Transfection in PS120/NHE3 fibroblasts with either NHERF or E3KARP reconstituted cAMP-induced inhibition of NHE3, resulting in 25\u201330% inhibition in these cells.\n          </jats:p>",
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