PXD049186-1

PXD049186 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics-directed manipulation reveals SEC22B as an hepatocellular signaling node governing metabolic actions of glucagon
Description	The peptide hormone glucagon is a fundamental metabolic regulator that is also being considered as a pharmocotherapeutic option for obesity and type 2 diabetes. Despite this, we know very little of how glucagon exerts its pleiotropic metabolic actions. Given that the liver is a chief site of action, we conducted in situ time-resolved liver phosphoproteomics to reveal glucagon signaling nodes. On pathway analysis of the thousands of phosphopeptides identified, we identified “vesicle transport” as a dominant signature with the vesicle trafficking protein SEC22 Homolog B (SEC22B) S137 phosphorylation being a top hit. Hepatocyte-specific loss- and gain-of-function experiments revealed that SEC22B was a key regulator of glycogen, lipid and amino acid metabolism, with SEC22B-S137 phosphorylation playing a major role in glucagon action. Mechanistically, we identified several protein binding partners of SEC22B affected by glucagon, some of which were only bound with SEC22B-S137 phosphorylation. In summary, here we demonstrate that phosphorylation of SEC22B is an hepatocellular signaling node mediating the metabolic actions of glucagon, and provide a rich resource for future investigations on the biology of glucagon action.
HostingRepository	PRIDE
AnnounceDate	2024-08-29
AnnouncementXML	Submission_2024-08-28_22:07:49.199.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ralf Schittenhelm
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-05 11:17:19	ID requested
⏵ 1	2024-08-28 22:07:49	announced
2	2024-10-22 06:56:55	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: SEC22B,liver, mass spectrometry, glucagon, phosphoproteomics

Adam Rose
contact affiliation	Nutrient Metabolism & Signalling Laboratory, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia
contact email	adam.rose@monash.edu
lab head
Ralf Schittenhelm
contact affiliation	Monash University
contact email	ralf.schittenhelm@monash.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049186
     1. Label: PRIDE project
     2. Name: Phosphoproteomics-directed manipulation reveals SEC22B as an hepatocellular signaling node governing metabolic actions of glucagon