Evidence map›Paper›PMID 25015294›Full record

ArticleJournal of cell science2014

Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics.

Sangmook Lee, Harish C Pant, Thomas B Shea

Open access · greenAbstract read
In one paragraph

Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Vasculocentric Axonal NfH in Small Vessel Disease.Journal of neuropathology and experimental neurology · 2022
    Article
  6. Article
  7. Review
  8. Axonal transport and neurological disease.Nature reviews. Neurology · 2019
    Review
  9. Article
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  11. Review
  12. Review
  13. Article
  14. Article
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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.

Sangmook LeeCenter for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA sangmook_lee@uml.edu PantH@ninds.nih.gov thomas_shea@uml.edu.
Harish C PantCytoskeletal Protein Regulation Section, NIH, NINDS, Bethesda, MD 20892, USA sangmook_lee@uml.edu PantH@ninds.nih.gov thomas_shea@uml.edu.
Thomas B SheaCenter for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA sangmook_lee@uml.edu PantH@ninds.nih.gov thomas_shea@uml.edu.
University of Massachusetts Lowell · US

Funding

Cyclin-dependent kinase 5 (Cdk5 physiology and pathology)ZIANS003104 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI PANT, HARISH C · 2009 to 2016
$9.6M
Role of a novel neuropeptide (p5/Tp5/TFp5) derived from a neuronal cell cycle kinase (Cdk5),p35 activator protein, in neurobiologyZIANS002725 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI PANT, HARISH C · 2009 to 2020
$9.6M
6 · The paper itself

Abstract

C-terminal neurofilament phosphorylation mediates cation-dependent self-association leading to neurofilament incorporation into the stationary axonal cytoskeleton. Multiple kinases phosphorylate the C-terminal domains of the heavy neurofilament subunit (NF-H), including cyclin-dependent protein kinase 5 (CDK5), mitogen-activated protein kinases (MAPKs), casein kinase 1 and 2 (CK1 and CK2) and glycogen synthase kinase 3β (GSK3β). The respective contributions of these kinases have been confounded because they phosphorylate multiple substrates in addition to neurofilaments and display extensive interaction. Herein, differentiated NB2a/d1 cells were transfected with constructs expressing GFP-tagged NF-H, isolated NF-H sidearms and NF-H lacking the distal-most 187 amino acids. Cultures were treated with roscovitine, PD98059, Li(+), D4476, tetrabromobenzotriazole and calyculin, which are active against CDK5, MKK1 (also known as MAP2K1), GSK3β, CK1, CK2 and protein phosphatase 1 (PP1), respectively. Sequential phosphorylation by CDK5 and GSK3β mediated the neurofilament-neurofilament associations. The MAPK pathway (i.e. MKK1 to ERK1/2) was found to downregulate GSK3β, and CK1 activated PP1, both of which promoted axonal transport and restricted neurofilament-neurofilament associations to axonal neurites. The MAPK pathway and CDK5, but not CK1 and GSK3β, inhibited neurofilament proteolysis. These findings indicate that phosphorylation of neurofilaments by the proline-directed MAPK pathway and CDK5 counterbalance the impact of phosphorylation of neurofilaments by the non-proline-directed CK1 and GSK3β.

Indexed as

AnimalsAxonal TransportAxonsCasein Kinase ICasein Kinase IICell Line, TumorGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaIntermediate FilamentsMiceMitogen-Activated Protein Kinase 3Phosphoprotein PhosphatasesPhosphorylationProtein KinasesCasein Kinase ICasein Kinase IIGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGsk3b protein, mouseMitogen-Activated Protein Kinase 3Phosphoprotein PhosphatasesProtein KinasesAxonal stabilityCytoskeletonKinaseNeurofilamentPhosphatase

Identifiers

PMID25015294
PMCPMC6519427
OpenAlexW2097158382

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.