PXD025076

PXD025076 is an original dataset announced via ProteomeXchange.

Title	Global Phosphoproteomics Reveals Molecular Networks in Systemic Lupus Erythematosus
Description	Systemic lupus erythematosus (SLE) is a systemic and heterogeneous autoimmune disease for which its treatment and phosphorylation-dependent regulatory mechanism remain elusive. Here, we aim to explore the molecular mechanism of phosphorylation regulation for SLE. We employed high-throughput Phosphoproteomics of peripheral blood mononuclear cells (PBMCs) from 126 patients with SLE remission stage (SLE_S), 70 patients with SLE active stage (SLE_A), 160 patients with RA, and 135 healthy controls (HC). An independent cohort that included 60 SLE_S, 35 SLE_A, 50 RA and 40 HC was used to validate the phosphosites via parallel reaction monitoring (PRM). We revealed upregulated pathways involved in cell adhesion and migration in patients with SLE (SLE_S and SLE_A) compared with HCs and RA. Expression pattern clustering analysis revealed several specifically upregulated phosphosites, and the leukocyte transendothelial migration was specifically enriched in SLE_A. We predicted several key kinases including MAP3Ks, MAP2Ks, IKKB and TBK1, and found that upregulated kinase activity is associated with increased phosphorylation of VCL, TLN1 and VAPB by kinases-substrate network analysis. These phosphorylated proteins also regulate the pathways related to cell adhesion and migration, and which have not been implicated in previous studies of SLE. Moreover, we validated these phosphosites with the same trend as 4D-LFQ data, including LCP1 S5, TLN1 S1201, TLN1 S1225, VCL S275 and VCL S579. In summary, the present study elucidates the changes of phosphosites, kinases and pathways in SLE, and may provide potentially novel targets for further mechanism exploration.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:39:51.584.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shuhui Meng
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-29 12:16:30	ID requested
1	2023-03-11 01:10:08	announced
⏵ 2	2023-11-14 08:39:55	announced	2023-11-14: Updated project metadata.

Li Y, Ma C, Liao S, Qi S, Meng S, Cai W, Dai W, Cao R, Dong X, Kr, ä, mer BK, Yun C, Hocher B, Hong X, Liu D, Tang D, He J, Yin L, Dai Y, Combined proteomics and single cell RNA-sequencing analysis to identify biomarkers of disease diagnosis and disease exacerbation for systemic lupus erythematosus. Front Immunol, 13():969509(2022) [pubmed]

submitter keyword: Phosproteomics

SLE remission stage

SLE active stage

Kinases

parallel reaction monitoring

Shuhui Meng
contact affiliation	Shenzhen People’s Hospital
contact email	msh1215@126.com
lab head
Shuhui Meng
contact affiliation	Shenzhen people's hospital
contact email	msh1215@126.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD025076

PRIDE project URI

• PRIDE
  1. PXD025076
     1. Label: PRIDE project
     2. Name: Global Phosphoproteomics Reveals Molecular Networks in Systemic Lupus Erythematosus