PXD047413

PXD047413 is an original dataset announced via ProteomeXchange.

Title	Endocannabinoid biosynthetic enzymes regulate pain response via LKB1–AMPK signaling
Description	Diacylglycerol lipase-beta (DAGLβ) serves as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme regulating endocannabinoid and eicosanoid metabolism in immune cells including macrophages and dendritic cells. Genetic or pharmacological inactivation of DAGLβ ameliorates inflammation and hyper-nociception in preclinical models of pathogenic pain. These beneficial effects have been assigned principally to reductions in downstream proinflammatory lipid signaling, leaving alternative mechanisms of regulation largely underexplored. Here, we apply quantitative chemical- and phospho-proteomics to find that disruption of DAGLβ in primary macrophages leads to LKB1–AMPK signaling activation, resulting in reprogramming of the phosphoproteome and bioenergetics. Notably, AMPK inhibition reversed the antinociceptive effects of DAGLβ blockade, thereby directly supporting DAGLβ–AMPK crosstalk in vivo. Our findings uncover signaling between endocannabinoid biosynthetic enzymes and ancient energy-sensing kinases to mediate cell biological and pain responses.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:51:39.306.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD047413
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Miaomiao Chen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	6x(13)C; 6x(13)C
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-30 12:45:58	ID requested
⏵ 1	2024-10-07 13:51:40	announced

10.6019/PXD047413;

10.1073/pnas.2304900120;

Chen M, Shin M, Ware TB, Donvito G, Muchhala KH, Mischel R, Mustafa MA, Serbulea V, Upchurch CM, Leitinger N, Akbarali HI, Lichtman AH, Hsu KL, Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling. Proc Natl Acad Sci U S A, 120(52):e2304900120(2023) [pubmed]

submitter keyword: inflammation, AMPK,endocannabinoids, diacylglycerol lipase, activity based protein profiling

Ku-lung Hsu
contact affiliation	Associate Professor Stephen F. and Fay Evans Martin Endowed Professorship in Chemistry CPRIT Scholar Department of Chemistry University of Texas at Austin
contact email	ken.hsu@austin.utexas.edu
lab head
Miaomiao Chen
contact affiliation	University of Virginia
contact email	mc5qu@virginia.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD047413

PRIDE project URI

• PRIDE
  1. PXD047413
     1. Label: PRIDE project
     2. Name: Endocannabinoid biosynthetic enzymes regulate pain response via LKB1–AMPK signaling