Evidence map›Paper›PMID 11744745›Full record

ArticleThe Journal of physiology2001

Phosphorylation of Ser(982) in the sodium bicarbonate cotransporter kNBC1 shifts the HCO(3)(-) : Na(+) stoichiometry from 3 : 1 to 2 : 1 in murine proximal tubule cells.

E Gross, K Hawkins, A Pushkin, P Sassani, R Dukkipati, N Abuladze, U Hopfer, I Kurtz

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in The Journal of physiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

34 citing papers in PubMed, 85 citations in OpenAlex.

  1. Inactivation mechanisms of NaCommunications biology · 2025
    Article
  2. Activation of the Ae4 (Slc4a9) cation-driven ClAmerican journal of physiology. Gastrointestinal and liver physiology · 2021
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Adenylyl cyclase 6 is required for maintaining acid-base homeostasis.Clinical science (London, England : 1979) · 2018
    Article
  8. Article
  9. Review
  10. Review
  11. Cation-coupled bicarbonate transporters.Comprehensive Physiology · 2014
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

E GrossDepartment of Urology, Case Western Reserve University and VA Medical Center, Cleveland, OH 44106, USA. ezg@po.cwru.edu
K Hawkins
A Pushkin
P Sassani
R Dukkipati
N Abuladze
U Hopfer
I Kurtz
University of California, Los Angeles · USCase Western Reserve University · USLouis Stokes Cleveland VA Medical Center · US

Funding

VASOACTIVE HORMONES: RECEPTORS AND SIGNALING MECHANISMSP01HL041618 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI HOPFER, ULRICH · 1989 to 2004
$6.7M
Duodenal Muscosal Defense MechanismsR01DK054221 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KAUNITZ, JONATHAN D. · 1999 to 2016
$4.4M
NA+ AND CL- TRANSPORT IN THE MAMMALIAN PROXIMAL TUBULER01DK046976 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KURTZ, IRA · 1997 to 2000
$187k
NHLBI NIH HHS HL-41618NHLBI NIH HHS P01 HL041618NIDDK NIH HHS DK46976NIDDK NIH HHS DK54221NIDDK NIH HHS DK6976NIDDK NIH HHS R01 DK054221
6 · The paper itself

Abstract

1. Adenosine 3',5'-cyclic monophosphate (cAMP) modulates proximal tubule sodium and bicarbonate absorption by decreasing the rate of apical Na(+)-H(+) exchange and basolateral sodium bicarbonate efflux, through activation of protein kinase A (PKA). The electrogenic sodium bicarbonate cotransporter kNBC1 mediates basolateral sodium and bicarbonate efflux in the proximal tubule by coupling the transport of 1 Na(+) cation to that of 3 HCO(3)(-) anions. In this work we studied the effects of cAMP on the function of kNBC1 expressed heterologously in a proximal tubule cell line. 2. A mouse renal proximal tubule cell line, deficient in electrogenic sodium bicarbonate cotransport function, was transfected with kNBC1. Cells were grown on a permeable support to confluence, mounted in an Ussing chamber and permeabilized apically with amphotericin B. Current through the cotransporter was isolated as the difference current due to the reversible inhibitor dinitrostilbene disulfonate. The HCO(3)(-) : Na(+) stoichiometry of kNBC1 was calculated from its reversal potential by measuring the current-voltage relationships of the cotransporter at different Na(+) concentration gradients. 3. Addition of the potent cAMP agonist 8-Br-cAMP caused the stoichiometry of kNBC1 to shift from 3 HCO(3)(-) : 1 Na(+) to 2 HCO(3)(-) : 1 Na(+). Pretreatment of the cells with the PKA inhibitor H-89 abolished the effect of the agonist on the stoichiometry change. Replacing Ser(982) at the C-terminus consensus PKA phosphorylation site with alanine resulted in a failure of PKA to phosphorylate the transporter and induce a stoichiometry shift. 4. Our data indicate that cAMP modulates the stoichiometry of kNBC1 through activation of PKA. The change in stoichiometry from 3 : 1 to 2 : 1 is predicted to cause a shift in the direction of basolateral membrane sodium bicarbonate transport from efflux to influx. Ser(982) in the C-terminus of kNBC1 is a target for PKA phosphorylation. This is the first example of modulation of the stoichiometry of a membrane transporter by phosphorylation.

Indexed as

Amino Acid SequenceAnimalsBicarbonatesCell LineChemical PhenomenaChemistryConsensus SequenceCyclic AMPCyclic AMP-Dependent Protein KinasesKidney Tubules, ProximalMathematicsMicePhosphorylationSodiumSodium-Bicarbonate SymportersBicarbonatesCyclic AMPCyclic AMP-Dependent Protein KinasesSodiumSodium-Bicarbonate Symporters

Identifiers

PMID11744745
PMCPMC2278987
OpenAlexW2080882597

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.