Evidence map›Paper›PMID 33554397›Full record

ArticleProtein science : a publication of the Protein Society2021

The interaction of p38 with its upstream kinase MKK6.

Ganesan Senthil Kumar, Rebecca Page, Wolfgang Peti

Open access · greenAbstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 32% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Exploring dysregulated miRNAs in ALS: implications for disease pathogenesis and early diagnosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Zoological research · 2025
    Article
  7. Article
  8. Article
  9. Linear motif specificity in signaling through p38α and ERK2 mitogen-activated protein kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  10. Article
  11. The interaction of p38 with its upstream kinase MKK6.Protein science : a publication of the Protein Society · 2021
    Article
  12. 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

3 authors at 1 institution in 1 country.

Ganesan Senthil KumarDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA.
Rebecca PageDepartment of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut, USA.
Wolfgang PetiDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA.ORCID 0000-0002-8830-6594
UConn Health · US

Funding

Dynamics & energetics of p38a kinase regulation by ligandsR01GM100910 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI PETI, WOLFGANG, WAND, A. JOSHUA · 2013 to 2016
$1.3M
NIGMS NIH HHS R01 GM100910NIGMS NIH HHS R01GM100910
6 · The paper itself

Abstract

Mitogen-activated protein kinase (MAPK; p38, ERK, and JNK) cascades are evolutionarily conserved signaling pathways that regulate the cellular response to a variety of extracellular stimuli, such as growth factors and interleukins. The MAPK p38 is activated by its specific upstream MAPK kinases, MKK6 and MKK3. However, a comprehensive molecular understanding of how these cognate upstream kinases bind and activate p38 is still missing. Here, we combine NMR spectroscopy and isothermal titration calorimetry to define the binding interface between full-length MKK6 and p38. It was shown that p38 engages MKK6 not only via its hydrophobic docking groove, but also influences helix αF, a secondary structural element that plays a key role in organizing the kinase core. It was also shown that, unlike MAPK phosphatases, the p38 conserved docking (CD) site is much less affected by MKK6 binding. Finally, it was demonstrated that these interactions with p38 are conserved independent of the MKK6 activation state. Together, the results revealed differences between specificity markers of p38 regulation by upstream kinases, which do not effectively engage the CD site, and downstream phosphatases, which require the CD site for productive binding.

Indexed as

Binding SitesEnzyme ActivationHumansMAP Kinase Kinase 6Nuclear Magnetic Resonance, Biomolecularp38 Mitogen-Activated Protein KinasesProtein Conformation, alpha-HelicalMAP2K6 protein, humanMAP Kinase Kinase 6p38 Mitogen-Activated Protein KinasesMKK6NMR spectroscopyp38 activationp38 MAP kinaseprotein:protein interactionSLiM

Identifiers

PMID33554397
PMCPMC7980501
OpenAlexW3128671779

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.