Evidence map›Paper›PMID 16507987›Full record

ArticleMolecular and cellular biology2006

PB1 domain-dependent signaling complex is required for extracellular signal-regulated kinase 5 activation.

Kazuhiro Nakamura, Mark T Uhlik, Nancy L Johnson, Klaus M Hahn, Gary L Johnson

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.4field-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

22 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Article
  3. Prediction of Protein-Protein Interactions Based on Domain.Computational and mathematical methods in medicine · 2019
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. MEK and the inhibitors: from bench to bedside.Journal of hematology & oncology · 2013
    Review
  11. Article
  12. MEK5/ERK5 pathway: the first fifteen years.Biochimica et biophysica acta · 2012
    Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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.

Kazuhiro NakamuraDepartment of Pharmacology, CB#7365, 1108 Mary Ellen Jones Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA.
Mark T Uhlik
Nancy L Johnson
Klaus M Hahn
Gary L Johnson
University of North Carolina at Chapel Hill · USUNC Lineberger Comprehensive Cancer Center

Funding

Function of MEKK3 and its osmosensing scaffold proteinR01GM068820 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHNSON, GARY L. · 2003 to 2015
$4.5M
RECEPTOR INTERACTION WITH GTP REGULATORY PROTEINSR37GM030324 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHNSON, GARY L. · 1999 to 2008
$3.7M
REGULATORY PROTEINS OF ADENYLATE CYCLASER01GM030324 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHNSON, GARY L. · 1985 to 2012
$1.8M
NIGMS NIH HHS GM30324NIGMS NIH HHS GM68820NIGMS NIH HHS R01 GM030324NIGMS NIH HHS R01 GM068820NIGMS NIH HHS R37 GM030324
6 · The paper itself

Abstract

MEKK2, MEK5, and extracellular signal-regulated kinase 5 (ERK5) are members of a three-kinase cascade for the activation of ERK5. MEK5 is the only MAP2K to express a PB1 domain, and we have shown that it heterodimerizes with the PB1 domain of MEKK2. Here we demonstrate the MEK5 PB1 domain is a scaffold that also binds ERK5, functionally forming a MEKK2-MEK5-ERK5 complex. Reconstitution assays and CFP/YFP imaging (fluorescence resonance energy transfer [FRET]) measuring YFP-MEKK2/CFP-MEK5 and CFP-MEK5/YFP-ERK5 interactions define distinct MEK5 PB1 domain binding sites for MEKK2 and ERK5, with a C-terminal extension of the PB1 domain contributing to ERK5 binding. Stimulus-dependent CFP/YFP FRET in combination with mutational analysis was used to define MEK5 PB1 domain residues critical for the interaction of MEKK2/MEK5 and MEK5/ERK5 required for activation of the ERK5 pathway in living cells. Fusion of the MEK5 PB1 domain to the N terminus of MEK1 confers ERK5 regulation by a MAP2K normally regulating only ERK1/2. The MEK5 PB1 domain confers stringent MAP3K regulation of ERK5 relative to more promiscuous MAP3K control of ERK1/2, JNK, and p38.

Indexed as

Signal TransductionAmino Acid SequenceAnimalsBacterial ProteinsCells, CulturedDimerizationEnzyme ActivationFluorescence Resonance Energy TransferGreen Fluorescent ProteinsLuminescent ProteinsMAP Kinase Kinase 5MAP Kinase Kinase Kinase 2Mitogen-Activated Protein Kinase 7Molecular Sequence DataMultiprotein ComplexesMutationBacterial ProteinsCyan Fluorescent ProteinGreen Fluorescent ProteinsLuminescent ProteinsMAP2K5 protein, humanMAP Kinase Kinase 5MAP Kinase Kinase Kinase 2Mitogen-Activated Protein Kinase 7Multiprotein ComplexesRecombinant ProteinsSorbitolyellow fluorescent protein, Bacteria

Identifiers

PMID16507987
PMCPMC1430298
OpenAlexW1969382272

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.