PXD026508

PXD026508 is an original dataset announced via ProteomeXchange.

Title	Withaferin A inhibits LFA-1-stimulated ZAP70 activity and T-cell motility
Description	a steroidal lactone withaferin A (WFA) can inhibit T-cell motility, which is crucial for adaptive immune responses as well as autoimmune reactions. Tandem mass spectrometry identified WFA-interactome in human T-cells that were stimulated to migrate via cross-linking of the lymphocyte function-associated antigen-1 (LFA-1) integrin with the ligand intercellular adhesion receptor 1 (ICAM-1). Data revealed significant enrichment of the zeta-chain-associated protein kinase 70 (ZAP70) and cytoskeletal actin protein interaction networks. Phospho-peptide mapping and kinome analysis substantiated kinase signaling downstream of ZAP70 and cytoskeletal kinase pathways as key WFA targets, which was further confirmed by in silico analysis and molecular assays. The WFA-ZAP70 complex was disrupted by a redox agent dithiothreitol, suggesting a covalent binding interface. Moreover, WFA ablated the phosphorylation of the myosin light chain, further constraining T-cell motility. These studies identify a mechanism whereby WFA can impact T-cell motility. WFA can therefore be exploited to pharmacologically controlling host immune responses and preventing autoimmune-mediated pathologies.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_08:55:03.104.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SoFong Cam Ngan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-06 22:12:11	ID requested
⏵ 1	2022-02-17 08:55:03	announced

Fazil MHUT, Chirumamilla CS, Perez-Novo C, Wong BHS, Kumar S, Sze SK, Vanden Berghe W, Verma NK, inhibiting the kinase ZAP70 and subsequent kinome signaling. J Biol Chem, 297(6):101377(2021) [pubmed]

submitter keyword: T-lymphocytes, migration, withaferin A, inflammation, kinome

Navin Kumar Verma
contact affiliation	Lee Kong Chian School of Medicine, Nanyang Technological University Singapore
contact email	nkverma@ntu.edu.sg
lab head
SoFong Cam Ngan
contact affiliation	Nanyang Technological University
contact email	sfcngan@ntu.edu.sg
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026508
     1. Label: PRIDE project
     2. Name: Withaferin A inhibits LFA-1-stimulated ZAP70 activity and T-cell motility