Evidence map›Paper›PMID 28365983›Full record

ArticleACS synthetic biology2017

Engineering Pak1 Allosteric Switches.

Onur Dagliyan, Andrei V Karginov, Sho Yagishita, Madeline E Gale, Hui Wang, Celine DerMardirossian, Claire M Wells, Nikolay V Dokholyan, Haruo Kasai, Klaus M Hahn

Open access · greenAbstract read
In one paragraph

Article in ACS synthetic biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

25 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Optogenetically engineered Septin-7 enhances immune cell infiltration of tumor spheroids.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Article
  9. Article
  10. Allosteric regulation of kinase activity in living cells.bioRxiv : the preprint server for biology · 2023
    Article
  11. Review
  12. Article
  13. Design and engineering of allosteric communications in proteins.Current opinion in structural biology · 2022
    Review
  14. Article
  15. Article
  16. Review
  17. Engineering an Allosteric Control of Protein Function.The journal of physical chemistry. B · 2021
    Review
  18. p21-Activated Kinase 1 Promotes Breast TumorigenesisFrontiers in cell and developmental biology · 2021
    Article
  19. Article
  20. Controlling protein conformation with light.Current opinion in structural biology · 2019
    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

10 authors at 1 institution in 3 countries.

Andrei V KarginovDepartment of Pharmacology, University of Illinois at Chicago , Chicago Illinois 60612, United States.
Sho YagishitaCenter for Disease Biology and Integrative Medicine, The University of Tokyo , Bunko-ku, Tokyo 113-0033, Japan.
Madeline E GaleDivision of Cancer Studies, King's College London , London SE1 1UL, England, U.K.
Hui Wang
Celine DerMardirossianDepartment of Cell and Molecular Biology, Scripps Research Institute , La Jolla, California 92037, United States.
Claire M WellsDivision of Cancer Studies, King's College London , London SE1 1UL, England, U.K.
Nikolay V Dokholyan
Haruo KasaiCenter for Disease Biology and Integrative Medicine, The University of Tokyo , Bunko-ku, Tokyo 113-0033, Japan.
Klaus M Hahn
University of North Carolina at Chapel Hill · US

Funding

INTERACTIVE GRAPHICS FOR MOLECULAR STUDIES &MICROSCOPYP41EB002025 · NIBIB · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SUPERFINE, RICHARD · 2003 to 2019
$16.9M
Mechanisms Of Cell Migration On 3D Aligned MatricesR01CA142833 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI FRIEDL, ANDREAS, HAHN, KLAUS M. · 2010 to 2020
$3.4M
Protein Misfolding and AggregationR01GM080742 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DOKHOLYAN, NIKOLAY · 2007 to 2015
$2.8M
Mechanisms of PAK1 activation, signaling and tumor resistanceR01CA175747 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J., HAHN, KLAUS M. · 2014 to 2018
$1.8M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA142833NCI NIH HHS R01 CA175747NIBIB NIH HHS P41 EB002025NIGMS NIH HHS R01 GM080742
6 · The paper itself

Abstract

P21-activated kinases (PAKs) are important regulators of cell motility and morphology. It has been challenging to interrogate their functions because cells adapt to genetic manipulation of PAK, and because inhibitors act on multiple PAK isoforms. Here we describe genetically encoded PAK1 analogues that can be selectively activated by the membrane-permeable small molecule rapamycin. An engineered domain inserted away from the active site responds to rapamycin to allosterically control activity of the PAK1 isoform. To examine the mechanism of rapamycin-induced PAK1 activation, we used molecular dynamics with graph theory to predict amino acids involved in allosteric communication with the active site. This analysis revealed allosteric pathways that were exploited to generate kinase switches. Activation of PAK1 resulted in transient cell spreading in metastatic breast cancer cells, and long-term dendritic spine enlargement in mouse hippocampal CA1 neurons.

Indexed as

Allosteric RegulationAnimalsCA1 Region, HippocampalCatalytic DomainCell Line, TumorCell MovementHippocampusHumansIn Vitro TechniquesMicep21-Activated KinasesRatsRats, Sprague-DawleySignal TransductionSirolimusp21-Activated KinasesSirolimusallosteric switchcell motilitydendritic spinesPAKprotein dynamics

Identifiers

PMID28365983
PMCPMC5562282
OpenAlexW2604304370

What Socratic 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 Socratic graph.