Evidence map›Paper›PMID 24790081›Full record

ArticleThe Journal of biological chemistry2014

Conserved modular domains team up to latch-open active protein kinase Cα.

Carter J Swanson, Michael Ritt, William Wang, Michael J Lang, Arvind Narayan, John J Tesmer, Margaret Westfall, Sivaraj Sivaramakrishnan

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. 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
2.3field-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, 25 citations in OpenAlex.

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  13. Patterning protein complexes on DNA nanostructures using a GFP nanobody.Protein science : a publication of the Protein Society · 2016
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  19. Tuning the signalling output of protein kinase C.Biochemical Society transactions · 2014
    Review
  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

8 authors at 1 institution in 1 country.

Carter J SwansonFrom the Biophysics Program.
Michael RittDepartment of Cell and Developmental Biology.
William WangDepartment of Cell and Developmental Biology, Department of Cardiac Surgery.
Michael J LangDepartment of Cell and Developmental Biology.
Arvind NarayanDepartment of Biomedical Engineering, Life Sciences Institute, and.
John J TesmerFrom the Biophysics Program, the Departments of Pharmacology and Biological Sciences, University of Michigan, Ann Arbor, Michigan 48109.
Margaret WestfallDepartment of Cardiac Surgery, Department of Biomedical Engineering, Life Sciences Institute, and.
Sivaraj SivaramakrishnanFrom the Biophysics Program, Department of Cell and Developmental Biology, Department of Biomedical Engineering, Life Sciences Institute, and sivaraj@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Structure, function, and inhibition of G protein-coupled receptor kinasesR01HL071818 · NHLBI · UNIVERSITY OF TEXAS AUSTIN · PI TESMER, JOHN · 2004 to 2023
$7.1M
Structural Studies of Galphaq and Its Complexes at the Cell MembraneR01HL086865 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESMER, JOHN · 2007 to 2015
$3.0M
The kinase toolbox: Mapping the spatial and temporal regulation of cell signalingDP2CA186752 · NCI · UNIVERSITY OF MINNESOTA · PI SIVARAMAKRISHNAN, SIVARAJ · 2013 to 2013
$2.3M
NCI NIH HHS 1DP2 CA186752-01NCI NIH HHS DP2 CA186752NHLBI NIH HHS R01 HL071818NHLBI NIH HHS R01 HL086865
6 · The paper itself

Abstract

Signaling proteins comprised of modular domains have evolved along with multicellularity as a method to facilitate increasing intracellular bandwidth. The effects of intramolecular interactions between modular domains within the context of native proteins have been largely unexplored. Here we examine intra- and intermolecular interactions in the multidomain signaling protein, protein kinase Cα (PKCα). We identify three interactions between two activated PKC molecules that synergistically stabilize a nanomolar affinity homodimer. Disruption of the homodimer results in a loss of PKC-mediated ERK1/2 phosphorylation, whereas disruption of the auto-inhibited state promotes the homodimer and prolongs PKC membrane localization. These observations support a novel regulatory mechanism wherein homodimerization dictates the equilibrium between the auto-inhibited and active states of PKC by sequestering auto-inhibitory interactions. Our findings underscore the physiological importance of context-dependent modular domain interactions in cell signaling.

Indexed as

AnimalsCell MembraneCHO CellsCricetinaeCricetulusHumansMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Protein Kinase C-alphaProtein MultimerizationProtein Structure, TertiarySignal TransductionMAPK1 protein, humanMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PRKCA protein, humanProtein Kinase C-alphaExtracellular Signal-regulated Kinase (ERK)Fluorescence Resonance Energy Transfer (FRET)HomodimerizationModular DomainsPKCProtein DomainProtein Kinase C (PKC)Protein-Protein Interaction

Identifiers

PMID24790081
PMCPMC4067214
OpenAlexW2001731514

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.