PXD012975

PXD012975 is an original dataset announced via ProteomeXchange.

Title	Endothelial PKA targets ATG16L1 to regulate angiogenesis by limiting autophagy
Description	The cAMP-dependent protein kinase A (PKA) regulates a plethora of cellular functions in health and disease. During angiogenesis, PKA activity in endothelial cells controls the transition from sprouting to vessel maturation and limits tip cell formation independently of Notch signaling. The molecular PKA targets mediating these effects remain unknown. We report a chemical genetics screen identifying endothelial-specific substrates of PKA in human umbilical vein endothelial cells (HUVEC). 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. The phosphorylations drive degradation of ATG16L1 protein. Knocking down PKA or inhibiting its activity increased ATG16L1 protein levels and endothelial autophagy. In vivo genetics and pharmacological experiments demonstrated that autophagy inhibition partially rescues vascular hypersprouting caused by PKA deficiency. We propose that endothelial PKA activity restricts active sprouting by reducing endothelial autophagy through phosphorylation of ATG16L1.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:50:06.753.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gunnar Dittmar
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-05 05:58:50	ID requested
1	2019-10-04 02:56:43	announced
⏵ 2	2023-11-14 08:50:07	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: autophagy, PKA, ATG16L1

Holger Gerhardt
contact affiliation	Max-Delbrück Center for molecular medicine Robert-Rössle Strasse 10 13125 Berlin
contact email	Holger.Gerhardt@mdc-berlin.de
lab head
Gunnar Dittmar
contact affiliation	LIH
contact email	gunnar.dittmar@lih.lu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012975
     1. Label: PRIDE project
     2. Name: Endothelial PKA targets ATG16L1 to regulate angiogenesis by limiting autophagy