Dataset Information

Phosphoproteomic studies of role of LAR protein tyrosine phosphatase in mouse embryonic fibroblasts

ABSTRACT: To gain insights into the signalling pathways regulated by Leukocyte common antigen-related protein (LAR), including those that are PDGF-dependent, we have carried out the first systematic analysis of LAR-regulated signal transduction using SILAC-based quantitative proteomic and phosphoproteomic techniques. We have analysed differential phosphorylation between wild-type mouse embryo fibroblasts (MEFs) or MEFS in which the LAR cytoplasmic phosphatase domains had been deleted (LARΔP).

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Disease Free

SUBMITTER: Debbie Cunningham

LAB HEAD: Debbie L Cunningham

PROVIDER: PXD002545 | Pride | 2016-04-15

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 268

Publications

Regulation of Platelet Derived Growth Factor Signaling by Leukocyte Common Antigen-related (LAR) Protein Tyrosine Phosphatase: A Quantitative Phosphoproteomics Study.

Sarhan Adil R AR Patel Trushar R TR Creese Andrew J AJ Tomlinson Michael G MG Hellberg Carina C Heath John K JK Hotchin Neil A NA Cunningham Debbie L DL

Molecular & cellular proteomics : MCP 20160413 6

Intracellular signaling pathways are reliant on protein phosphorylation events that are controlled by a balance of kinase and phosphatase activity. Although kinases have been extensively studied, the role of phosphatases in controlling specific cell signaling pathways has been less so. Leukocyte common antigen-related protein (LAR) is a member of the LAR subfamily of receptor-like protein tyrosine phosphatases (RPTPs). LAR is known to regulate the activity of a number of receptor tyrosine kinase ...[more]

PMID: 27074791

Similar Datasets

Project description:Although-synuclein is implicated in the pathogenesis of Parkinson’s disease and related disorders, it remains unclear whether specific conformations or levels of-synuclein assemblies are toxic and how they cause progressive loss of human dopaminergic neurons. To address this issue, we used iPSC-derived dopaminergic neurons with -synuclein triplication or controls where endogenous -synuclein was imprinted into synthetic or disease-relevant conformations. We used -synuclein fibrils generated de novo or amplified from homogenates of brains affected with Parkinson’s disease (n=3) or multiple system atrophy (n=5). We found that a 2.5-fold increase in -synuclein levels in -synuclein gene triplication neurons promoted seeded aggregation in a dose and time-dependent fashion, which was associated with a further increase in -synuclein gene expression. Progressive neuronal loss was observed only in -synuclein triplication neurons seeded with brain-amplified fibrils. Transcriptomic analysis and isogenic correction of -synuclein triplication revealed that intraneuronal-synuclein levels solely and sufficiently explained vulnerability to neuronal death. Proximity-dependent biotinylation in living cells identified 56 differentially interacting proteins with endogenously assembled -synuclein including evasion of Parkinson’s disease-associated deglycase DJ-1 by aggregates triggered with brain amplified fibrils. Knockout of DJ-1 and related glyoxalase-1 in cell lines increased -synuclein aggregation. Similarly, methylglyoxal treatment or CRISPR/Cas9 knockout of DJ-1 in iPSC-derived dopaminergic neurons enhanced fibril-induced aggregation and cell death. Thus, toxicity of -synuclein strains depends on aggregate burden, which is determined by monomer levels and conformation which dictates differential interactomes. Our results define parameters for iPSC-based modellingof -synuclein pathology using brain amplified fibrils and demonstrate how Parkinson’s disease-associated genes influence the phenotypic manifestation of strains in human neurons.

			Action	DRS
	Maxquantoutput.zip	Other
	phospho_exp1_1.raw	Raw
	phospho_exp1_10.raw	Raw
	phospho_exp1_11.raw	Raw
	phospho_exp1_12.raw	Raw