Evidence map›Paper›PMID 35829702›Full record

ArticleThe Journal of cell biology2022

Dissecting protein tyrosine phosphatase signaling by engineered chemogenetic control of its activity.

Jordan Fauser, Vincent Huyot, Jacob Matsche, Barbara N Szynal, Yuri Alexeev, Pradeep Kota, Andrei V Karginov

Open access · greenAbstract read
In one paragraph

Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 42% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. 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

7 authors at 3 institutions in 1 country.

Jordan FauserDepartment of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL.ORCID 0000-0002-0675-8977
Vincent HuyotDepartment of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL.
Jacob MatscheDepartment of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL.ORCID 0000-0003-4743-0297
Barbara N SzynalDepartment of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL.
Yuri AlexeevArgonne National Laboratory, Lemont, IL.ORCID 0000-0001-5066-2254
Pradeep KotaMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.ORCID 0000-0002-2825-5123
Andrei V KarginovDepartment of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL.ORCID 0000-0003-2370-6383
University of Illinois Chicago · USArgonne National Laboratory · USUniversity of North Carolina at Chapel Hill · US

Funding

TRAINING PROGRAM IN LUNG BIOLOGY AND PATHOBIOLOGYT32HL007829 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DOLLY MEHTA · 1995 to 2026
$15.6M
Synthetic Biology and Optogenetics CoreP01HL151327 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI REHMAN, JALEES · 2021 to 2025
$11.8M
Src-mediated pathways regulating adherens junction assembly.R01GM118582 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARGINOV, ANDREI V · 2017 to 2021
$1.8M
Engineered regulation of tyrosine phosphatase activity in living cellsR21CA212907 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARGINOV, ANDREI V · 2017 to 2019
$683k
Optogenetic tools for the dissection of oncogenic signaling mediated by kinasesR21CA223915 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARGINOV, ANDREI V, REHMAN, JALEES · 2018 to 2020
$580k
NCI NIH HHS R21 CA212907NCI NIH HHS R21 CA223915NHLBI NIH HHS P01 HL151327NHLBI NIH HHS T32 HL007829NIGMS NIH HHS R01 GM118582
6 · The paper itself

Abstract

Protein tyrosine phosphatases (PTPases) are critical mediators of dynamic cell signaling. A tool capable of identifying transient signaling events downstream of PTPases is essential to understand phosphatase function on a physiological time scale. We report a broadly applicable protein engineering method for allosteric regulation of PTPases. This method enables dissection of transient events and reconstruction of individual signaling pathways. Implementation of this approach for Shp2 phosphatase revealed parallel MAPK and ROCK II dependent pathways downstream of Shp2, mediating transient cell spreading and migration. Furthermore, we show that the N-SH2 domain of Shp2 regulates MAPK-independent, ROCK II-dependent cell migration. Engineered targeting of Shp2 activity to different protein complexes revealed that Shp2-FAK signaling induces cell spreading whereas Shp2-Gab1 or Shp2-Gab2 mediates cell migration. We identified specific transient morphodynamic processes induced by Shp2 and determined the role of individual signaling pathways downstream of Shp2 in regulating these events. Broad application of this approach is demonstrated by regulating PTP1B and PTP-PEST phosphatases.

Indexed as

Protein Tyrosine Phosphatase, Non-Receptor Type 11Signal TransductionAllosteric RegulationCell MovementFocal Adhesion Kinase 1MAP Kinase Signaling Systemrho-Associated KinasesFocal Adhesion Kinase 1Protein Tyrosine Phosphatase, Non-Receptor Type 11rho-Associated Kinases

Identifiers

PMID35829702
PMCPMC9284425
OpenAlexW4285088502

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.