Evidence map›Paper›PMID 39333498›Full record

ArticleNature communications2024

Phosphoproteomics-directed manipulation reveals SEC22B as a hepatocellular signaling node governing metabolic actions of glucagon.

Yuqin Wu, Ashish Foollee, Andrea Y Chan, Susanne Hille, Jana Hauke, Matthew P Challis, Jared L Johnson, Tomer M Yaron, Victoria Mynard, Okka H Aung and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. iScience · 2026
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Yuqin WuNutrient Metabolism & Signalling Laboratory, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria, Australia.ORCID 0000-0002-1762-1896
Ashish FoolleeNutrient Metabolism & Signalling Laboratory, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria, Australia.
Andrea Y ChanNutrient Metabolism & Signalling Laboratory, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria, Australia.
Susanne HilleDepartment of Internal Medicine V, University Hospital of Schleswig-Holstein, Campus Kiel, Germany.ORCID 0000-0002-9809-4636
Jana HaukeDivision of Inherited Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
Matthew P ChallisDepartment of Biochemistry and Molecular Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing & Health Sciences, Monash University, Victoria, Australia.
Jared L JohnsonMeyer Cancer Center, Weill Cornell Medicine, New York, USA.ORCID 0000-0003-1802-6527
Tomer M YaronMeyer Cancer Center, Weill Cornell Medicine, New York, USA.
Victoria MynardNutrient Metabolism & Signalling Laboratory, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria, Australia.
Okka H AungNutrient Metabolism & Signalling Laboratory, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria, Australia.
Maria Almira S CleofeNutrient Metabolism & Signalling Laboratory, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria, Australia.
Cheng HuangDepartment of Biochemistry and Molecular Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing & Health Sciences, Monash University, Victoria, Australia.ORCID 0000-0002-4575-1233
Terry C C Lim Kam SianMonash Proteomics and Metabolomics Platform, Monash University, Victoria, Australia.ORCID 0000-0001-7038-1214
Mohammad RahbariGerman Cancer Research Center (DKFZ), Division of Chronic Inflammation and Cancer, Im Neuenheimer Feld 280, Heidelberg, Germany.ORCID 0000-0003-1133-2134
Suchira GallageGerman Cancer Research Center (DKFZ), Division of Chronic Inflammation and Cancer, Im Neuenheimer Feld 280, Heidelberg, Germany.ORCID 0000-0002-1956-3597
Mathias HeikenwalderGerman Cancer Research Center (DKFZ), Division of Chronic Inflammation and Cancer, Im Neuenheimer Feld 280, Heidelberg, Germany.ORCID 0000-0002-3135-2274
Lewis C CantleyMeyer Cancer Center, Weill Cornell Medicine, New York, USA.ORCID 0000-0002-1298-7653
Ralf B SchittenhelmDepartment of Biochemistry and Molecular Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing & Health Sciences, Monash University, Victoria, Australia.ORCID 0000-0001-8738-1878
Luke E FormosaDepartment of Biochemistry and Molecular Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing & Health Sciences, Monash University, Victoria, Australia.ORCID 0000-0002-7740-6151
Greg C SmithSchool of Biomedical Sciences, University of New South Wales, Sydney, Australia.
Jürgen G OkunDivision of Inherited Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
Oliver J MüllerDepartment of Internal Medicine V, University Hospital of Schleswig-Holstein, Campus Kiel, Germany.ORCID 0000-0001-8223-2638
Patricia M RusuNutrient Metabolism & Signalling Laboratory, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria, Australia.ORCID 0000-0001-7210-1976
Adam J RoseNutrient Metabolism & Signalling Laboratory, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria, Australia. adam.rose@monash.edu.ORCID 0000-0001-9132-8244

Funding

Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
Role of Phosphoinositides and Protein Kinases in the control of Cancer MetabolismR35CA197588 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEWIS C. CANTLEY · 2016 to 2026
$10.2M
Diabetes Australia Research Trust (DART) Y22GNCI NIH HHS P01 CA120964NCI NIH HHS R35 CA197588
6 · The paper itself

Abstract

The peptide hormone glucagon is a fundamental metabolic regulator that is also being considered as a pharmacotherapeutic option for obesity and type 2 diabetes. Despite this, we know very little regarding how glucagon exerts its pleiotropic metabolic actions. Given that the liver is a chief site of action, we performed in situ time-resolved liver phosphoproteomics to reveal glucagon signaling nodes. Through pathway analysis of the thousands of phosphopeptides identified, we reveal "membrane trafficking" 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 reveal 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 identify several protein binding partners of SEC22B affected by glucagon, some of which were differentially enriched with SEC22B-S137 phosphorylation. In summary, we demonstrate that phosphorylation of SEC22B is a hepatocellular signaling node mediating the metabolic actions of glucagon and provide a rich resource for future investigations on the biology of glucagon action.

Indexed as

GlucagonHepatocytesProteomicsSignal TransductionAnimalsGlycogenHumansLipid MetabolismLiverMaleMiceMice, Inbred C57BLPhosphoproteinsPhosphorylationVesicular Transport ProteinsGlucagonGlycogenPhosphoproteinsVesicular Transport Proteins

Identifiers

PMID39333498
PMCPMC11436942

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.