Evidence mapPaperPMID 39823198Full record

ArticleAmerican journal of physiology. Renal physiology2025

Ribosomal s6 kinase is a mediator of aquaporin-2 S256 phosphorylation and membrane accumulation after EGFR inhibition with erlotinib.

Richard S E Babicz, Noah Baylor, Abby Terlouw, Daphne A Faber, Kazuhiko Fukushima, Ricardo M Biondi, Richard Bouley, Dennis Brown

Abstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
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

4 citing papers in PubMed.

  1. Diurnal function and expression of aquaporins in the mouse kidney.American journal of physiology. Renal physiology · 2025
    Article
  2. Article
  3. Expanding Mechanistic Insights into Urinary Concentrating Ability.Journal of the American Society of Nephrology : JASN · 2025
    Article
  4. 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

8 authors.

Richard S E BabiczDivision of Nephrology, Program in Membrane Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States.ORCID 0009-0004-4896-4367
Noah BaylorDivision of Nephrology, Program in Membrane Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States.
Abby TerlouwDivision of Nephrology, Program in Membrane Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States.
Daphne A FaberDivision of Nephrology, Program in Membrane Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States.ORCID 0009-0006-9795-9681
Kazuhiko FukushimaDivision of Nephrology, Program in Membrane Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States.
Ricardo M BiondiInstituto de Investigación en Biomedicina de Buenos Aires (IBioBA) - CONICET - Partner Institute of the Max Planck SocietyBuenos AiresArgentina.ORCID 0000-0002-8873-7167
Richard BouleyDivision of Nephrology, Program in Membrane Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States.ORCID 0000-0003-0443-0756
Dennis BrownDivision of Nephrology, Program in Membrane Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States.ORCID 0000-0002-5011-7798

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · 1991 to 2025
$10.1M
PILOT AND FEASIBILITY (P/F) PROGRAMP30DK057521 · MASSACHUSETTS GENERAL HOSPITAL · 2000 to 2005
$8.2M
P&F programP30DK135043 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$1.1M
Cell Biology of Vasopressin-induced Water ChannelsR01DK096586 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$618k
American Society of Nephrology (ASN)HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DK043351HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DK057521HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DK096586HHS | NIH | NIH Office of the Director (OD) 1S10OD021577-01HHS | NIH | NIH Office of the Director (OD) 1S10OD032211-01NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK057521NIDDK NIH HHS P30 DK135043NIDDK NIH HHS R01 DK096586NIH HHS S10 OD021577NIH HHS S10 OD032211
6 · The paper itself

Abstract

Vasopressin (VP) activates protein kinase A (PKA), resulting in phosphorylation events and membrane accumulation of aquaporin-2 (AQP2). Epidermal growth factor receptor (EGFR) inhibition with erlotinib also induces AQP2 membrane trafficking with a phosphorylation pattern similar to VP, but without increasing PKA activity. Here, we identify the ribosomal s6 kinase (RSK) as a major mediator phosphorylating AQP2 in this novel, erlotinib-induced pathway. We found that RSK was expressed in collecting duct principal cells in rat kidneys. RSK inhibition with BI-D1870 blocked erlotinib-induced AQP2 serine 256 (S256) phosphorylation and membrane accumulation. CRISPR-generated RSK knockout (KO) cells failed to show increased S256 phosphorylation in response to erlotinib. Like PKA, RSK was able to phosphorylate AQP2 S256 in vitro. Inhibition of phosphoinositide-dependent kinase-1 (PDK1), a known activator of RSK, blocked erlotinib-induced AQP2 S256 phosphorylation and membrane accumulation. We conclude that RSK is a crucial terminal kinase phosphorylating AQP2 at S256 upon EGFR inhibition by erlotinib.

Indexed as

Aquaporin 2Cell MembraneErbB ReceptorsErlotinib HydrochlorideKidney Tubules, CollectingProtein Kinase InhibitorsRibosomal Protein S6 KinasesAnimalsHumansMalePhosphorylationRatsRats, Sprague-DawleySignal TransductionVasopressinsAqp2 protein, ratAquaporin 2Egfr protein, ratErbB ReceptorsErlotinib HydrochlorideProtein Kinase InhibitorsRibosomal Protein S6 KinasesVasopressinsaquaporin-2EGFRepithelial transportvasopressinvesicle trafficking

Identifiers

PMID39823198
PMCPMC12228059

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.