Evidence map›Paper›PMID 31580256›Full record

ArticleeLife2019

Endothelial PKA activity regulates angiogenesis by limiting autophagy through phosphorylation of ATG16L1.

Xiaocheng Zhao, Pavel Nedvetsky, Fabio Stanchi, Anne-Clemence Vion, Oliver Popp, Kerstin Zühlke, Gunnar Dittmar, Enno Klussmann, Holger Gerhardt

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

20 citing papers in PubMed, 41 citations in OpenAlex.

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  12. Review
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  16. Article
  17. Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  18. Article
  19. Autophagy in the Regulation of Tissue Differentiation and Homeostasis.Frontiers in cell and developmental biology · 2020
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 4 countries.

Xiaocheng ZhaoVascular Patterning Laboratory, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID https://orcid.org/0000-0002-4048-6813
Pavel NedvetskyVascular Patterning Laboratory, Center for Cancer Biology, VIB, Leuven, Belgium.
Fabio StanchiVascular Patterning Laboratory, Center for Cancer Biology, VIB, Leuven, Belgium.
Anne-Clemence VionIntegrative Vascular Biology Lab, Max-Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.ORCID http://orcid.org/0000-0002-2788-2512
Oliver PoppProteomics, Max-Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Kerstin ZühlkeAnchored Signaling Lab, Max-Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Gunnar DittmarProteomics, Max-Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Enno KlussmannAnchored Signaling Lab, Max-Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.ORCID http://orcid.org/0000-0003-4004-5003
Holger GerhardtVascular Patterning Laboratory, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID https://orcid.org/0000-0002-3030-0384
Max Delbrück Center · DEVIB-KU Leuven Center for Cancer Biology · BEInserm · FR

Funding

Bundesministerium für Bildung und Forschung 16GW0179KBundes Ministerium für Bildung und Forschung 16GW0179KDeutsche Forschungsgemeinschaft 394046635 - SFB 1365Deutsche Forschungsgemeinschaft DFG KL1415/7-1Else-Kroener Stiftung 2014_A26European Research Council 311719 REshapeEuropees Fonds voor Regionale Ontwikkeling G.0742.15NFonds vor Wetenschappelijk Onderzoek G.0742.15NVIB Tech Watch Q3 2015Vlaams Instituut voor Biotechnologie Tech Watch Q3 2015
6 · The paper itself

Abstract

The cAMP-dependent protein kinase A (PKA) regulates various cellular functions in health and disease. In endothelial cells PKA activity promotes vessel maturation and limits tip cell formation. Here, we used a chemical genetic screen to identify endothelial-specific direct substrates of PKA in human umbilical vein endothelial cells (HUVEC) that may mediate these effects. Amongst several candidates, we identified ATG16L1, a regulator of autophagy, as novel target of PKA. Biochemical validation, mass spectrometry and peptide spot arrays revealed that PKA phosphorylates ATG16L1α at Ser268 and ATG16L1β at Ser269, driving phosphorylation-dependent degradation of ATG16L1 protein. Reducing PKA activity increased ATG16L1 protein levels and endothelial autophagy. Mouse in vivo genetics and pharmacological experiments demonstrated that autophagy inhibition partially rescues vascular hypersprouting caused by PKA deficiency. Together these results indicate that endothelial PKA activity mediates a critical switch from active sprouting to quiescence in part through phosphorylation of ATG16L1, which in turn reduces endothelial autophagy.

Indexed as

AutophagyNeovascularization, PhysiologicProtein Processing, Post-TranslationalAnimalsAutophagy-Related ProteinsCell LineCyclic AMP-Dependent Protein KinasesEndothelial CellsHumansMicePhosphorylationATG16L1 protein, humanAtg16l1 protein, mouseAutophagy-Related ProteinsCyclic AMP-Dependent Protein Kinasesangiogenesisautophagybiochemistrycell biologychemical biologychemical geneticshumanmouseprotein kinase A

Identifiers

PMID31580256
PMCPMC6797479
OpenAlexW2978203685

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.