Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identifying a GSK3-TRARG1 signaling axis reveals BCL9L as a novel regulator of GLUT4 trafficking

ABSTRACT: The trafficking regulator of GLUT4-1 (TRARG1) protein positively regulates insulin-stimulated GLUT4 trafficking. Here we identify post-translational modifications on TRARG1 and identify that GSK3 is the upstream kinase responsible for TRARG1 phosphorylation at Serines 72, 76, and 80. We employ affinity enrichment mass spectrometry to identify protein interactions regulated by TRARG1 phosphorylation.

INSTRUMENT(S): Q Exactive HF-X, Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Fat Cell

SUBMITTER: Sean Humphrey

LAB HEAD: David E James

PROVIDER: PXD022765 | Pride | 2022-08-12

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20171024_QEplus_BP_Xiaowen_TRARG1_1.raw	Raw
	20171024_QEplus_BP_Xiaowen_TRARG1_2.raw	Raw
	20171024_QEplus_BP_Xiaowen_TRARG1_3.raw	Raw
	20171024_QEplus_BP_Xiaowen_TRARG1_4.raw	Raw
	20171024_QEplus_BP_Xiaowen_TRARG1_5.raw	Raw

Items per page:

1 - 5 of 25

Publications

Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.

Duan Xiaowen X Norris Dougall M DM Humphrey Sean J SJ Yang Pengyi P Cooke Kristen C KC Bultitude Will P WP Parker Benjamin L BL Conway Olivia J OJ Burchfield James G JG Krycer James R JR Brodsky Frances M FM James David E DE Fazakerley Daniel J DJ

The Biochemical journal 20220601 11

Trafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical and mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a novel substrate for GSK3. Priming phosphorylation of murine TRARG1 at serine 84 allows for GSK3-directed phosphorylation at serines 72, 76 and 80. A similar ...[more]

PMID: 35594055

Similar Datasets

Regulatory phosphorylation of eIF6 by GSK3

Project description:The overall goal of this project is to determine the key sites in the C-terminus of eIF6 that are recognized and phosphorylated by GSK3. Analysis of kinase reactions using the site-specific mutants as well as the C-terminus deletion mutants of eIF6 indicated that there are GSK3-specific motifs in the C-terminus that are phosphorylated by GSK3. The purpose of the Mass Spectrometry studies is to use MS as a targeted and secondary approach to validate and identify GSK3-specific sites of phosphorylation in the C-terminus of eIF6.

2020-06-16 | MSV000085596 | MassIVE

Phosphoproteomics reveals the GSK3-PDX1 axis as a key pathogenic signaling node in diabetic islets

Project description:Progressive decline of pancreatic beta cell function is central to the pathogenesis of type 2 diabetes. Protein phosphorylation regulates glucose-stimulated insulin secretion from beta cells, but how signaling networks are remodeled in diabetic islets in vivo remains unknown. Using high-sensitivity mass spectrometry-based proteomics we quantified 6,500 proteins and 13,000 phosphopeptides in islets of obese diabetic mice and matched controls, revealing drastic remodeling of key kinase hubs and signaling pathways. Integration with a literature-derived signaling network implicated GSK3 kinase in the control of the beta cell-specific transcription factor PDX1. Deep phosphoproteomic analysis of human islets chronically treated with high glucose demonstrated a conserved glucotoxicity-dependent role of GSK3 kinase in regulating insulin secretion. Remarkably, the ability of beta cells to secrete insulin in response to glucose was rescued almost completely by pharmacological inhibition of GSK3. Thus, our resource enables investigation of mechanisms and drug targets in type 2 diabetes.

2019-03-15 | PXD012671 | Pride

Adipose Rab10 Knockout Causes Insulin Resistance through Impaired Glucose Uptake

Project description:Insulin action in adipocytes affects whole-body insulin sensitivity. Studies of adipose-specific Glut4 knockout mice have established that adipose Glut4 contributes to the control of systemic glucose homeostasis. Presumably, this reflects a role for Glut4-mediated glucose transport in the regulation of secreted adipokines. In cultured 3T3-L1 adipocytes, Rab10 GTPase is required for insulin-stimulated translocation of Glut4 (Sano et al., 2007). The physiological importance of adipose Rab10 and the significance of its role in the control of Glut4 vesicle trafficking in vivo are unknown. Here we report that adipocytes from adipose-specific Rab10 knockout mice have a ~50% reduction in glucose uptake and Glut4 translocation to the cell surface in response to insulin, demonstrating a role for Rab10 in Glut4 trafficking. Moreover, hyperinsulinemic-euglycemic clamp shows decreased whole-body glucose uptake as well as impaired suppression of hepatic glucose production in adipose Rab10 knockout mice. Thus, fully functional Glut4 vesicle trafficking in adipocytes is critical for maintaining insulin sensitivity. Comparative transcriptome analysis of perigonadal adipose tissue demonstrates significant transcriptional similarities between adipose Rab10 knockout mice and adipose Glut4 knockout mice, consistent with the notion that the phenotypic similarities between the two models are mediated by reduced insulin-stimulated glucose transport into adipocytes. Transcriptome sequencing of perigonadal white adipose tissue

2016-06-30 | E-GEOD-70123 | biostudies-arrayexpress

Polyubiquitination analysis upon GSK3 inhibition in HeLa cell extracts

Project description:HeLa cell extracts with or without GSK3 enzyme inhibition were assayed using protein microarrays in order to detect GSK3-dependent changes in protein polyubiquitination.

2014-05-15 | GSE50629 | GEO

Adipose Rab10 Knockout Causes Insulin Resistance through Impaired Glucose Uptake

2016-06-30 | GSE70123 | GEO

Effect of TUNAR silencing and GSK3 inhibition on human b-cell transcriptome

Project description:The aim of the study is to identify the target genes of long noncoding RNA TUNAR in human EndoC-βH1 cells with or without treatment of GSK3 inhibitor.

2017-06-01 | GSE99503 | GEO

RNA sequencing to identify common targets for GSK3

Project description:common targets with different GSK3 inhibition approaches

2017-07-10 | GSE84302 | GEO

miRNA analysis to identify common targets for GSK3

Project description:common targets with different GSK3 inhibition approaches

2017-07-06 | GSE84100 | GEO

GSK3 phosphorylation sites in Lpd

Project description:Neural crest cells are multipotent cells that delaminate from the neuroepithelium, migrating throughout the embryo. Aberrant migration causes developmental defects. Animal models are improving our understanding of neural crest anomalies, but in vivo migration behaviours are poorly understood. Here, we demonstrate that murine neural crest cells display actin-based lamellipodia and filopodia in vivo. Using neural crest-specific knockouts or inhibitors, we show that the serine-threonine kinase Glycogen Synthase Kinase-3 (GSK3), and the cytoskeletal regulator Lamellipodin (Lpd), are required for lamellipodia formation whilst preventing focal adhesion maturation. Lpd is a novel substrate of GSK3 and phosphorylation of Lpd favours interactions with the Scar/WAVE complex (lamellipodia formation) at the expense of VASP and Mena interactions (adhesion maturation and filopodia formation). This improved understanding of cytoskeletal regulation in mammalian neural crest migration has general implications for neural crest anomalies and cancer.

2023-10-05 | PXD044150 | Pride

Polyubiquitination analysis upon GSK3 inhibition in HeLa cell extracts

Project description:HeLa cell extracts with or without GSK3 enzyme inhibition were assayed using protein microarrays in order to detect GSK3-dependent changes in protein polyubiquitination. HeLa lysates in triplicates were supplemented with ubiquitin and incubated on protein microarrays (ProtoArray 5.0; Invitrogen) in the presence or absence of the GSK3 inhibitor SB-216763. Polyubiquitination of the arrayed proteins was detected using specific antibodies. ProtoArray 5.0 contains over 9,000 full-length human proteins purified and arrayed in duplicate under native conditions to maximize functionality.

2014-05-15 | E-GEOD-50629 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data