Evidence map›Paper›PMID 32881857›Full record

ArticlePLoS biology2020

Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.

Jason Z Zhang, Andy H Nguyen, Shigeki Miyamoto, Joan Heller Brown, Andrew D McCulloch, Jin Zhang

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 40% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Jason Z ZhangDepartment of Bioengineering, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0003-0091-6273
Andy H NguyenDepartment of Bioengineering, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0002-3046-0409
Shigeki MiyamotoDepartment of Pharmacology, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0002-1513-8067
Joan Heller BrownDepartment of Pharmacology, University of California San Diego, La Jolla, California, United States of America.
Andrew D McCullochDepartment of Bioengineering, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0002-1708-5675
Jin ZhangDepartment of Bioengineering, University of California San Diego, La Jolla, California, United States of America.ORCID 0000-0001-7145-7823
University of California San Diego · US

Funding

Live-cell Activity Architecture in CancerR35CA197622 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2015 to 2026
$11.2M
Mechanisms of Compartmentalized cAMP SignalingR01DK073368 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2006 to 2026
$7.6M
RhoA mediated survival signals in cardiomyocytesR37HL028143 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER · 2010 to 2019
$4.0M
Systems Biology of Hypertrophic Heart Disease from Molecular Pathways to Organ SystemR01HL137100 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MCCULLOCH, ANDREW D. · 2017 to 2020
$2.0M
Cardiomyocyte CaM kinase II as a driver of cardiac inflammation and remodelingR01HL145459 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, MIYAMOTO, SHIGEKI · 2019 to 2022
$1.6M
The Virtual Cell: a Computational Resource for Collaborative Modeling and Simulation of Cell BiologyR24GM134211 · NIGMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI LOEW, LESLIE M · 2019 to 2019
$528k
NCI NIH HHS R35 CA197622NHLBI NIH HHS R01 HL137100NHLBI NIH HHS R37 HL028143NIDDK NIH HHS R01 DK073368NIGMS NIH HHS R24 GM134211
6 · The paper itself

Abstract

The small GTPase RhoA is a central signaling enzyme that is involved in various cellular processes such as cytoskeletal dynamics, transcription, and cell cycle progression. Many signal transduction pathways activate RhoA-for instance, Gαq-coupled Histamine 1 Receptor signaling via Gαq-dependent activation of RhoGEFs such as p63. Although multiple upstream regulators of RhoA have been identified, the temporal regulation of RhoA and the coordination of different upstream components in its regulation have not been well characterized. In this study, live-cell measurement of RhoA activation revealed a biphasic increase of RhoA activity upon histamine stimulation. We showed that the first and second phase of RhoA activity are dependent on p63 and Ca2+/PKC, respectively, and further identified phosphorylation of serine 240 on p115 RhoGEF by PKC to be the mechanistic link between PKC and RhoA. Combined approaches of computational modeling and quantitative measurement revealed that the second phase of RhoA activation is insensitive to rapid turning off of the receptor and is required for maintaining RhoA-mediated transcription after the termination of the receptor signaling. Thus, two divergent pathways enable both rapid activation and persistent signaling in receptor-mediated RhoA signaling via intricate temporal regulation.

Indexed as

AnimalsCalcium SignalingCells, CulturedEnzyme ActivationHeLa CellsHistamineHumansMicePhosphorylationProtein Kinase CReceptors, HistaminerhoA GTP-Binding ProteinRho Guanine Nucleotide Exchange FactorsSignal TransductionHistamineProtein Kinase CReceptors, HistaminerhoA GTP-Binding ProteinRHOA protein, humanRho Guanine Nucleotide Exchange Factors

Identifiers

PMID32881857
PMCPMC7494096
OpenAlexW3083135850

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.