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PXD047413

PXD047413 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEndocannabinoid biosynthetic enzymes regulate pain response via LKB1–AMPK signaling
DescriptionDiacylglycerol 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-07
AnnouncementXMLSubmission_2024-10-07_13:51:39.306.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD047413
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterMiaomiao Chen
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList6x(13)C; 6x(13)C
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-11-30 12:45:58ID requested
12024-10-07 13:51:40announced
Publication List
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]
Keyword List
submitter keyword: inflammation, AMPK,endocannabinoids, diacylglycerol lipase, activity based protein profiling
Contact List
Ku-lung Hsu
contact affiliationAssociate Professor Stephen F. and Fay Evans Martin Endowed Professorship in Chemistry CPRIT Scholar Department of Chemistry University of Texas at Austin
contact emailken.hsu@austin.utexas.edu
lab head
Miaomiao Chen
contact affiliationUniversity of Virginia
contact emailmc5qu@virginia.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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