PXD062325-1

PXD062325 is an original dataset announced via ProteomeXchange.

Title	Macrophage PAK2 controls the SIRPα immune checkpoint via cytoskeletal dynamics and endocytic trafficking
Description	Professional phagocytes are essential for immunomodulation, antimicrobial control, and initiation and resolution of inflammation. These cells rely on dynamic cytoskeletal rearrangements to respond to their environment. This plasticity requires a network of positive and negative regulators to control biomechanics and signaling circuits. P21-activated kinases (PAKs) regulate the actomyosin cytoskeleton, cell proliferation, and gene expression, yet their contributions to phagocyte functions remain unresolved. Analyzing PAK1/2-deficient phagocytes and utilizing a PAK inhibitor we show that PAK2 governs physio-mechanical macrophage properties, leading to membrane expansion, hyperphagic behavior and disruption of endocytic transport when absent, while PAKs cooperate to restrain oxidative neutrophil responses. In PAK1/mPAK2 ablated mice cytoskeletal remodeling combined with low-grade chronic inflammation prompts the spontaneous development of a macrophage-driven hematologic malignancy. Macrophage PAK2 ablation or inhibition markedly enhances cancer cell uptake by exerting biophysical control over the CD47-SIRPα checkpoint, indicating that biomechanical modification of macrophages holds promise in cancer immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2025-11-01
AnnouncementXML	Submission_2025-10-31_17:30:34.328.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kieran Wynne
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-27 15:50:47	ID requested
⏵ 1	2025-10-31 17:30:34	announced

Dataset with its publication pending

submitter keyword: PAK2, endocytic trafficking., SIRPα immune checkpoint,Macrophage

Prof Ulla Knaus
contact affiliation	Professor Of Immunobiology, University College Dublin, School of Medicine, Conway Institute Belfield Dublin 4. SFI Stokes Professor, Professor of Immunobiology, School of Medicine, Conway Institute, UCD, Ireland. Adjunct Professor, Dept of Immunology & Microbial Science, Scripps Research, La Jolla,CA, USA
contact email	ulla.knaus@ucd.ie
lab head
Kieran Wynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
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/2025/10/PXD062325

PRIDE project URI

• PRIDE
  1. PXD062325
     1. Label: PRIDE project
     2. Name: Macrophage PAK2 controls the SIRPα immune checkpoint via cytoskeletal dynamics and endocytic trafficking