PXD041902

PXD041902 is an original dataset announced via ProteomeXchange.

Title	WNK1 signalling regulates amino acid transport and mTORC1 activity to sustain AML growth
Description	The lack of curative therapies for acute myeloid leukaemia (AML) remains an ongoing challenge despite recent advances in the understanding of the molecular basis of the disease. Here we identify the WNK1-OXSR1/STK39 pathway as a previously uncharacterised dependency in AML. We show that genetic depletion and pharmacological inhibition of WNK1 or its downstream phosphorylation targets OXSR1 and STK39 strongly reduce cell proliferation and induce apoptosis in leukemic cells in vitro and in vivo. Furthermore, we show that the WNK1-OXSR1/STK39 pathway controls mTOR signalling via regulating amino acid uptake through a mechanism involving the phosphorylation of amino acid transporters, such as SLC38A2. Our results demonstrate a critical role of the WNK1-OXSR1/STK39 pathway in regulating amino acid uptake and in AML maintenance. Moreover, our mode of action studies suggests that WNK1 and OXSR1/STK39 inhibitors could be effective in a broad range of cancer types.
HostingRepository	PRIDE
AnnounceDate	2025-06-02
AnnouncementXML	Submission_2025-06-01_16:24:08.786.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Shliaha
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-01 04:44:17	ID requested
⏵ 1	2025-06-01 16:24:09	announced

Duan S, Agger K, Messling JE, Nishimura K, Han X, Pe, ñ, a-R, ø, mer I, Shliaha P, Damhofer H, Douglas M, Kohli M, Pal A, Asad Y, Van Dyke A, Reilly R, K, ö, chl R, Tybulewicz VLJ, Hendrickson RC, Raynaud FI, Gallipoli P, Poulogiannis G, Helin K, WNK1 signalling regulates amino acid transport and mTORC1 activity to sustain acute myeloid leukaemia growth. Nat Commun, 16(1):4920(2025) [pubmed]

10.1038/s41467-025-59969-8;

submitter keyword: WNK1, phosphoproteomics, AML, mTOR

Ronald Hendrickson
contact affiliation	Memorial Sloan Kettering Cancer Center
contact email	hendricr@mskcc.org
lab head
Pavel Shliaha
contact affiliation	MRC London Institute of Medical Sciences proteomics and metabolomics core
contact email	pavel.shliaha@gmail.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/2025/06/PXD041902

PRIDE project URI

• PRIDE
  1. PXD041902
     1. Label: PRIDE project
     2. Name: WNK1 signalling regulates amino acid transport and mTORC1 activity to sustain AML growth