Evidence map›Paper›PMID 18657070›Full record

ArticleTraffic (Copenhagen, Denmark)2008

Endosomal targeting of MEK2 requires RAF, MEK kinase activity and clathrin-dependent endocytosis.

Emilia Galperin, Alexander Sorkin

Open access · bronzeAbstract read
In one paragraph

Article in Traffic (Copenhagen, Denmark), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.5field-weighted citation impact, top 21% 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

30 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Review
  3. Atypical p38 Signaling, Activation, and Implications for Disease.International journal of molecular sciences · 2021
    Review
  4. Article
  5. Article
  6. Role for ERK1/2-dependent activation of FCHSD2 in cancer cell-selective regulation of clathrin-mediated endocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  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

2 authors at 1 institution in 1 country.

Emilia GalperinDepartment of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.
Alexander Sorkin
University of Colorado Denver · US

Funding

UNDERSTANDING THE MOLECULAR BASIS OF EPIGENETIC TRANSCRIPTIONAL SILENCINGP20RR020171 · NCRR · UNIVERSITY OF KENTUCKY · PI LOUIS HERSH, LOUIS HERSH LOUIS HERSH · 2004 to 2011
$16.5M
PATHOGENESIS OF CANCER--ROLE OF EGF RECEPTOR ENDOCYTOSISR01CA089151 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SORKIN, ALEXANDER D · 2001 to 2023
$6.9M
Receptor Tyrosine Kinase Signaling NetworksR01GM059570 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI HOEK, JOANNES B · 2000 to 2010
$3.6M
Regulation of MAP Activity by EGFR EndocytosisK99CA126161 · NCI · UNIVERSITY OF COLORADO DENVER · PI GALPERIN, EMILIA · 2008 to 2009
$212k
MECHANISM OF GROWTH FACTOR RECEPTOR ENDOCYTOSISR29DK046817 · NIDDK · VANDERBILT UNIVERSITY · PI SORKIN, ALEXANDER D · 1994 to 1999
–
NCI NIH HHS CA089151-08NCI NIH HHS K99 CA126161NCI NIH HHS R01 CA089151NCRR NIH HHS P20 RR020171NIDDK NIH HHS R29 DK046817NIGMS NIH HHS GM059570NIGMS NIH HHS R01 GM059570
6 · The paper itself

Abstract

To study spatiotemporal regulation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2) signaling cascade in living cells, a HeLa cell line in which MAPK kinase of ERK kinase (MEK) 2 (MAPK kinase) was knocked down by RNA interference and replaced with the green fluorescent protein (GFP)-tagged MEK2 was generated. In these cells, MEK2-GFP was stably expressed at a level similar to that of the endogenous MEK2 in the parental cells. Upon activation of the EGF receptor (EGFR), a pool of MEK2-GFP was found initially translocated to the plasma membrane and then accumulated in a subset of early and late endosomes. However, activated MEK was detected only at the plasma membrane and not in endosomes. Surprisingly, MEK2-GFP endosomes did not contain active EGFR, suggesting that endosomal MEK2-GFP was separated from the upstream signaling complexes. Knockdown of clathrin by small interfering RNA (siRNA) abolished MEK2 recruitment to endosomes but resulted in increased activation of ERK without affecting the activity of MEK2-GFP. The accumulation of MEK2-GFP in endosomes was also blocked by siRNA depletion of RAF kinases and by the MEK1/2 inhibitor, UO126. We propose that the recruitment of MEK2 to endosomes can be a part of the negative feedback regulation of the EGFR-MAPK signaling pathway by endocytosis.

Indexed as

Blotting, WesternCell MembraneClathrinEndocytosisEndosomesErbB ReceptorsFluorescent Antibody TechniqueGreen Fluorescent ProteinsHeLa CellsHumansMAP Kinase Kinase 2Mitogen-Activated Protein KinasesPhosphorylationProtein BindingProtein Transportraf KinasesClathrinErbB ReceptorsGreen Fluorescent ProteinsMAP2K2 protein, humanMAP Kinase Kinase 2Mitogen-Activated Protein Kinasesraf KinasesRecombinant Fusion ProteinsRNA, Small Interfering

Identifiers

PMID18657070
PMCPMC2750913
OpenAlexW1965458495

What OpenQuestion 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 OpenQuestion graph.