Evidence map›Paper›PMID 25253241›Full record

ArticleAmerican journal of physiology. Renal physiology2014

Akt recruits Dab2 to albumin endocytosis in the proximal tubule.

Kelly Koral, Hui Li, Nandita Ganesh, Morris J Birnbaum, Kenneth R Hallows, Elif Erkan

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Human Disabled-2 regulates thromboxane ANature communications · 2024
    Article
  5. Albumin Nanoparticle-Based Drug Delivery Systems.International journal of nanomedicine · 2024
    Review
  6. Emerging roles of proximal tubular endocytosis in renal fibrosis.Frontiers in cell and developmental biology · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Renal Handling of Albumin-From Early Findings to Current Concepts.International journal of molecular sciences · 2021
    Review
  11. Article
  12. The Journal of biological chemistry · 2018
    Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. 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

6 authors at 4 institutions in 1 country.

Kelly KoralDivision of Nephrology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania;
Hui LiDivision of Renal-Electrolyte, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
Nandita GaneshDivision of Nephrology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania;
Morris J BirnbaumInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Kenneth R HallowsDivision of Renal-Electrolyte, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
Elif ErkanDivision of Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Elif.Erkan@cchmc.org.
Children's Hospital of Pittsburgh · USUniversity of Pittsburgh · USCincinnati Children's Hospital Medical Center · USUniversity of Pennsylvania · US

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JACKSON, EDWIN KERRY · 2008 to 2022
$13.4M
Proteomics CoreP50DK096418 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI DEVARAJAN, PRASAD · 2012 to 2021
$8.4M
THE ROLE OF THE AKT/PKB SIGNALING IN INSULIN ACTIONR01DK056886 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BIRNBAUM, MORRIS J · 2000 to 2014
$5.3M
Mechanisms and Relevance of Sodium Transport Regulation by AMPKR01DK075048 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HALLOWS, KENNETH R · 2007 to 2015
$2.5M
Linking endocytosis to cell signaling in proteinuria induced tubular apoptosisK08DK083510 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ERKAN, ELIF · 2009 to 2011
$414k
NCATS NIH HHS UL1 TR000005NIDDK NIH HHS K08 DK083510NIDDK NIH HHS P30 DK 079307NIDDK NIH HHS P30 DK079307NIDDK NIH HHS P50 DK096418NIDDK NIH HHS R01 DK056886NIDDK NIH HHS R01 DK075048NIDDK NIH HHS R01 DK56886
6 · The paper itself

Abstract

Proximal tubule epithelial cells have a highly sophisticated endocytic machinery to retrieve the albumin in the glomerular filtrate. The megalin-cubilin complex and the endocytic adaptor disabled-2 (Dab2) play a pivotal role in albumin endocytosis. We previously demonstrated that protein kinase B (Akt) regulates albumin endocytosis in the proximal tubule through an interaction with Dab2. Here, we examined the nature of Akt-Dab2 interaction. The pleckstrin homology (PH) and catalytic domains (CD) of Akt interacted with the proline-rich domain (PRD) of Dab2 based on yeast-two hybrid (Y2H) experiments. Pull-down experiments utilizing the truncated constructs of Dab2 demonstrated that the initial 11 amino acids of Dab2-PRD were sufficient to mediate the interaction between Akt and Dab2. Endocytosis experiments utilizing Akt1- and Akt2-silencing RNA revealed that both Akt1 and Akt2 mediate albumin endocytosis in proximal tubule epithelial cells; therefore, Akt1 and Akt2 may play a compensatory role in albumin endocytosis. Furthermore, both Akt isoforms phosphorylated Dab2 at Ser residues 448 and 449. Ser-to-Ala mutations of these Dab2 residues inhibited albumin endocytosis and resulted in a shift in location of Dab2 from the peripheral to the perinuclear area, suggesting the physiological relevance of these phosphorylation sites in albumin endocytosis. We conclude that both Akt1 and Akt2 are involved in albumin endocytosis, and phosphorylation of Dab2 by Akt induces albumin endocytosis in proximal tubule epithelial cells. Further delineation of how Akt affects expression/phosphorylation of endocytic adaptors and receptors will enhance our understanding of the molecular network triggered by albumin overload in the proximal tubule.

Indexed as

EndocytosisAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAlbuminsAnimalsApoptosis Regulatory ProteinsHEK293 CellsHumansKidney Tubules, ProximalMaleMice, KnockoutPhosphorylationProtein BindingProtein Interaction Domains and MotifsProtein Interaction MappingProto-Oncogene Proteins c-aktAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAKT1 protein, humanAkt1 protein, mouseAKT2 protein, humanAkt2 protein, mouseAlbuminsApoptosis Regulatory ProteinsDAB2 protein, humanDab2 protein, mouseProto-Oncogene Proteins c-aktTumor Suppressor Proteinsalbuminendocytosisproximal tubule epithelial cells

Identifiers

PMID25253241
PMCPMC4269696
OpenAlexW2330359364

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.