Evidence map›Paper›PMID 12407081›Full record

ArticleThe Journal of general physiology2002

Regulation of AE2-mediated Cl- transport by intracellular or by extracellular pH requires highly conserved amino acid residues of the AE2 NH2-terminal cytoplasmic domain.

A K Stewart, M N Chernova, B E Shmukler, S Wilhelm, S L Alper

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of general physiology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 65 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. CK2 is a key regulator of SLC4A2-mediated ClPflugers Archiv : European journal of physiology · 2017
    Article
  8. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2016
    Article
  9. Article
  10. Article
  11. SLC4A transporters.Current topics in membranes · 2012
    Article
  12. Article
  13. Pendrin function and regulation in Xenopus oocytes.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2011
    Article
  14. Article
  15. Regulated transport of sulfate and oxalate by SLC26A2/DTDST.American journal of physiology. Cell physiology · 2010
    Article
  16. Article
  17. Protons make tumor cells move like clockwork.Pflugers Archiv : European journal of physiology · 2009
    Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

A K StewartDepartment of Medicine, Harvard Medical School, Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
M N Chernova
B E Shmukler
S Wilhelm
S L Alper
Beth Israel Deaconess Medical Center · USHarvard University · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAYNE I LENCER · 1986 to 2026
$32.4M
MOLECULAR PHYSIOLOGY OF BAND 3 LIKE PROTEINS OF KIDNEYR37DK043495 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ALPER, SETH LEO · 1998 to 2007
$3.0M
MOLECULAR PHYSIOLOGY OF BAND 3-LIKE PROTEINS OF KIDNEYR01DK043495 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ALPER, SETH LEO · 1991 to 1997
–
NIDDK NIH HHS DK34854NIDDK NIH HHS DK43495NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R37 DK043495Wellcome Trust
6 · The paper itself

Abstract

We reported recently that regulation by intracellular pH (pH(i)) of the murine Cl-/HCO(3)(-) exchanger AE2 requires amino acid residues 310-347 of the polypeptide's NH(2)-terminal cytoplasmic domain. We have now identified individual amino acid residues within this region whose integrity is required for regulation of AE2 by pH. 36Cl- efflux from AE2-expressing Xenopus oocytes was monitored during variation of extracellular pH (pH(o)) with unclamped or clamped pH(i), or during variation of pH(i) at constant pH(o). Wild-type AE2-mediated 36Cl- efflux was profoundly inhibited by acid pH(o), with a value of pH(o50) = 6.87 +/- 0.05, and was stimulated up to 10-fold by the intracellular alkalinization produced by bath removal of the preequilibrated weak acid, butyrate. Systematic hexa-alanine [(A)6]bloc substitutions between aa 312-347 identified the greatest acid shift in pH(o(50)) value, approximately 0.8 pH units in the mutant (A)6 342-347, but only a modest acid-shift in the mutant (A)6 336-341. Two of the six (A)6 mutants retained normal pH(i) sensitivity of 36Cl- efflux, whereas the (A)6 mutants 318-323, 336-341, and 342-347 were not stimulated by intracellular alkalinization. We further evaluated the highly conserved region between aa 336-347 by alanine scan and other mutagenesis of single residues. Significant changes in AE2 sensitivity to pH(o) and to pH(i) were found independently and in concert. The E346A mutation acid-shifted the pH(o(0) value to the same extent whether pH(i) was unclamped or held constant during variation of pH(o). Alanine substitution of the corresponding glutamate residues in the cytoplasmic domains of related AE anion exchanger polypeptides confirmed the general importance of these residues in regulation of anion exchange by pH. Conserved, individual amino acid residues of the AE2 cytoplasmic domain contribute to independent regulation of anion exchange activity by pH(o) as well as pH(i).

Indexed as

Anion Transport ProteinsAntiportersAcidsAmino Acid SequenceAmino Acid SubstitutionAnimalsBiological Transport, ActiveChloride-Bicarbonate AntiportersConserved SequenceCytoplasmFemaleHydrogen-Ion ConcentrationIon TransportKineticsMembrane ProteinsMutagenesis, Site-DirectedAcidsAnion Transport ProteinsAntiportersChloride-Bicarbonate AntiportersMembrane ProteinsSLC4A Proteins

Identifiers

PMID12407081
PMCPMC2229549
OpenAlexW2159926333

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.