Evidence map›Paper›PMID 28636945›Full record

ArticleCell reports2017

PKN1 Directs Polarized RAB21 Vesicle Trafficking via RPH3A and Is Important for Neutrophil Adhesion and Ischemia-Reperfusion Injury.

Qianying Yuan, Chunguang Ren, Wenwen Xu, Björn Petri, Jiasheng Zhang, Yong Zhang, Paul Kubes, Dianqing Wu, Wenwen Tang

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

19 citing papers in PubMed, 32 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

9 authors at 2 institutions in 2 countries.

Qianying YuanDepartment of Pharmacology, Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT 06520, USA.
Chunguang RenDepartment of Pharmacology, Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT 06520, USA.
Wenwen XuDepartment of Pharmacology, Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT 06520, USA.
Björn PetriSnyder Institute for Chronic Diseases Mouse Phenomics Resource Laboratory, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Jiasheng ZhangDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Yong ZhangDepartment of Pharmacology, Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT 06520, USA.
Paul KubesSnyder Institute for Chronic Diseases Mouse Phenomics Resource Laboratory, University of Calgary, Calgary, AB T2N 4N1, Canada.
Dianqing WuDepartment of Pharmacology, Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: dan.wu@yale.edu.
Wenwen TangDepartment of Pharmacology, Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: wenwen.tang@yale.edu.
Yale University · USUniversity of Calgary · CA

Funding

Yale/NIDA Neuroproteomics Research CenterP30DA018343 · NIDA · YALE UNIVERSITY · PI ANGUS C. NAIRN, Kenneth Robert WILLIAMS · 2004 to 2026
$37.1M
Signaling mechanisms and functions related to patho-physiology of vascular, lung and blood systemsR35HL135805 · NHLBI · YALE UNIVERSITY · PI WU, DIANQING · 2017 to 2023
$6.4M
Signaling Mechanisms for Leukocyte Migration RegulationR01HL108430 · NHLBI · YALE UNIVERSITY · PI WU, DIANQING · 2011 to 2016
$2.4M
Sustained signaling for fibroblast migrationR01HL120465 · NHLBI · YALE UNIVERSITY · PI WU, DIANQING · 2013 to 2016
$1.6M
Investigating cellular function and biochemical mechanism for STK24-CCM3 complexR01GM109487 · NIGMS · YALE UNIVERSITY · PI BOGGON, TITUS JONATHON, WU, DIANQING · 2014 to 2017
$1.3M
NHLBI NIH HHS R01 HL108430NHLBI NIH HHS R01 HL120465NHLBI NIH HHS R35 HL135805NIDA NIH HHS P30 DA018343NIGMS NIH HHS R01 GM109487
6 · The paper itself

Abstract

Polarized vesicle transport plays an important role in cell polarization, but the mechanisms underlying this process and its role in innate immune responses are not well understood. Here, we describe a phosphorylation-regulated polarization mechanism that is important for neutrophil adhesion to endothelial cells during inflammatory responses. We show that the protein kinase PKN1 phosphorylates RPH3A, which enhances binding of RPH3A to guanosine triphosphate (GTP)-bound RAB21. These interactions are important for polarized localization of RAB21 and RPH3A in neutrophils, which leads to PIP5K1C90 polarization. Consistent with the roles of PIP5K1C90 polarization, the lack of PKN1 or RPH3A impairs neutrophil integrin activation, adhesion to endothelial cells, and infiltration in inflammatory models. Furthermore, myeloid-specific loss of PKN1 decreases tissue injury in a renal ischemia-reperfusion model. Thus, this study characterizes a mechanism for protein polarization in neutrophils and identifies a potential protein kinase target for therapeutic intervention in reperfusion-related tissue injury.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCell AdhesionCell PolarityFemaleKidneyMaleMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsNeutrophilsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein Kinase CProtein Processing, Post-TranslationalProtein Transport1-phosphatidylinositol-4-phosphate 5-kinaseAdaptor Proteins, Signal TransducingNerve Tissue ProteinsPhosphotransferases (Alcohol Group Acceptor)Protein Kinase Cprotein kinase Nrab21 protein, mouserab GTP-Binding ProteinsRabphilin-3AVesicular Transport Proteinsadhesionneutrophil polarizationPIP5K1C90PKN1RAB21renal ischemia-reperfusionRPH3Avesicle trafficking

Identifiers

PMID28636945
PMCPMC5548392
OpenAlexW2691733691

What OpenQuestion 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 OpenQuestion graph.