Evidence map›Paper›PMID 26004360›Full record

ArticleDevelopmental biology2015

Polo-like kinase 2 regulates angiogenic sprouting and blood vessel development.

Hongbo Yang, Longhou Fang, Rui Zhan, Jeffrey M Hegarty, Jie Ren, Tzung K Hsiai, Joseph G Gleeson, Yury I Miller, JoAnn Trejo, Neil C Chi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Polo-like kinase2 regulates renal tubulointerstitial fibrosis via notch signaling pathway in diabetic kidney disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  4. Article
  5. Esm-1 mediates transcriptional polarization associated with diabetic kidney disease.American journal of physiology. Renal physiology · 2024
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Rap1 in endothelial biology.Current opinion in hematology · 2017
    Review
  14. 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

10 authors at 3 institutions in 1 country.

Hongbo YangDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093-0613J, USA.
Longhou FangDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093-0613J, USA.
Rui ZhanDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093-0613J, USA.
Jeffrey M HegartyDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093-0613J, USA.
Jie RenDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093-0613J, USA.
Tzung K HsiaiDivision of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA, USA; Department of Bioengineering, School of Engineering & Applied Science, University of California, Los Angeles, CA, USA.
Joseph G GleesonNeurogenetics Laboratory, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
Yury I MillerDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093-0613J, USA.
JoAnn TrejoDepartment of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Neil C ChiDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093-0613J, USA; Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: nchi@ucsd.edu.
University of California San Diego · USHoward Hughes Medical Institute · USUniversity of California, Los Angeles · US

Funding

Project 3. Genetic Models of Human Structural Brain Defects in ZebrafishP01HD070494 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2011 to 2016
$6.7M
Micro-Sensors to Study Electrical and Mechanical Coupling of Injured MyocardiumR01HL111437 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HSIAI, TZUNG K, XU, XIAOLEI · 2012 to 2020
$3.1M
Zebrafish models of vascular inflammation and atherosclerosisR01HL093767 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILLER, YURY · 2009 to 2014
$2.5M
Directed Cardiac Cellular Programming: A New Paradigm for Cardiac RegenerationDP2OD007464 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C · 2010 to 2010
$2.3M
Electrical Biophysical Forces Impact Cardiac MorphogenesisR01HD069305 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C · 2011 to 2015
$1.6M
NHLBI NIH HHS HL093767NHLBI NIH HHS HL111437NHLBI NIH HHS R01 HL093767NHLBI NIH HHS R01 HL111437NICHD NIH HHS HD069305NICHD NIH HHS HD070494NICHD NIH HHS P01 HD070494NICHD NIH HHS R01 HD069305NIH HHS DP2 OD007464
6 · The paper itself

Abstract

Angiogenesis relies on specialized endothelial tip cells to extend toward guidance cues in order to direct growing blood vessels. Although many of the signaling pathways that control this directional endothelial sprouting are well known, the specific cellular mechanisms that mediate this process remain to be fully elucidated. Here, we show that Polo-like kinase 2 (PLK2) regulates Rap1 activity to guide endothelial tip cell lamellipodia formation and subsequent angiogenic sprouting. Using a combination of high-resolution in vivo imaging of zebrafish vascular development and a human umbilical vein endothelial cell (HUVEC) in vitro cell culture system, we observed that loss of PLK2 function resulted in a reduction in endothelial cell sprouting and migration, whereas overexpression of PLK2 promoted angiogenesis. Furthermore, we discovered that PLK2 may control angiogenic sprouting by binding to PDZ-GEF to regulate RAP1 activity during endothelial cell lamellipodia formation and extracellular matrix attachment. Consistent with these findings, constitutively active RAP1 could rescue the endothelial cell sprouting defects observed in zebrafish and HUVEC PLK2 knockdowns. Overall, these findings reveal a conserved PLK2-RAP1 pathway that is crucial to regulate endothelial tip cell behavior in order to ensure proper vascular development and patterning in vertebrates.

Indexed as

AnimalsCell LineCell MovementCell ProliferationGuanine Nucleotide Exchange FactorsHumansHuman Umbilical Vein Endothelial CellsNeovascularization, PhysiologicNerve Tissue ProteinsProtein Serine-Threonine KinasesPseudopodiarap1 GTP-Binding ProteinsRNA InterferenceRNA, Small InterferingSignal TransductionZebrafishGuanine Nucleotide Exchange FactorsNerve Tissue ProteinsPLK2 protein, humanProtein Serine-Threonine Kinasesrap1 GTP-Binding ProteinsRAPGEF2 protein, humanRNA, Small InterferingAngiogenesisHuman umbilical vein endothelial cellsPolo-like kinase 2Vascular developmentZebrafish

Identifiers

PMID26004360
PMCPMC4515213
OpenAlexW349758587

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.