PXD025208

PXD025208 is an original dataset announced via ProteomeXchange.

Title	BioID-screening identifies PEAK1 and SHP2 as components of the Alk “proximitome” in neuroblastoma cells
Description	Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that is mutated in approximately 10% of pediatric cancer neuroblastoma (NB). To shed light on ALK-driven signaling processes, we employed BioID-based in vivo proximity labeling to identify molecules that interact with ALK. NB cells expressing inducible ALK-BirA* fusion proteins were generated and stimulated with ALKAL ligands in the presence and absence of the ALK tyrosine kinase inhibitor (TKI) lorlatinib. LC/MS-MS analysis identified multiple proteins, including PEAK1 and SHP2, which were validated as ALK interactors in NB cells. Further analysis of the ALK-SHP2 interaction confirmed that the ALK-SHP2 interaction as well as SHP2-Y542 phosphorylation was dependent on ALK activation. Use of the SHP2 inhibitors, SHP099 and RMC-4550, resulted in inhibition of cell growth in ALK-driven NB cells. In addition, we noted a strong synergistic effect of combined ALK and SHP2 inhibition that was specific to ALK-driven NB cells, suggesting a potential therapeutic option for ALK-driven NB.
HostingRepository	PRIDE
AnnounceDate	2025-08-21
AnnouncementXML	Submission_2025-08-21_12:34:46.625.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Proteomics Core Facility
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-06 04:19:26	ID requested
⏵ 1	2025-08-21 12:34:47	announced

10.1016/j.jmb.2021.167158;

U, ç, kun E, Siaw JT, Guan J, Anthonydhason V, Fuchs J, Wolfstetter G, Hallberg B, Palmer RH, BioID-Screening Identifies PEAK1 and SHP2 as Components of the ALK Proximitome in Neuroblastoma Cells. J Mol Biol, 433(19):167158(2021) [pubmed]

submitter keyword: SHP099, lorlatinib, RMC-4550,BirA*, signaling

Ruth Palmer
contact affiliation	Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine at the Sahlgrenska Academy, University of Gothenburg, Sweden.
contact email	ruth.palmer@gu.se
lab head
Proteomics Core Facility
contact affiliation	SAMBIO Core Facilities, Sahgrenska Academy, University of Gothenburg
contact email	gupcf@outlook.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/2025/08/PXD025208

PRIDE project URI

• PRIDE
  1. PXD025208
     1. Label: PRIDE project
     2. Name: BioID-screening identifies PEAK1 and SHP2 as components of the Alk “proximitome” in neuroblastoma cells