PXD024806-1

PXD024806 is an original dataset announced via ProteomeXchange.

Title	Inference of Kinase-Signaling Networks in Human Myeloid Cell Line Models by Phosphoproteomics using Kinase Activity Enrichment Analysis (KAEA)
Description	Despite the indisputable efficacy of kinase-inhibitors in myeloid malignancies, cure remains an exception and most patients eventually progress. Therefore, there is an unmet clinical need in developing diagnostic pipelines for the characterization of kinase-activities and signaling networks to investigate their implications in response and resistance. Here, we used the BCR-ABL1 driven K562 and hetero-/homozygote FLT3-ITD driven MOLM13/MV4-11 human myeloid cell line models exposed to the clinically established BCR-ABL1 and FLT3 kinase-inhibitors, Nilotinib and Midostaurin, respectively. Titanium dioxide enrichment with liquid chromatography tandem mass spectrometry (LC-MS) was used and the differential phosphoproteomics profiles analyzed with the Kinase-Activity Enrichment Analysis (KAEA) pipeline. This novel pipeline allows inferring kinase activities within signaling networks. We observed correct detection of expected direct (ABL, KIT, SRC) and indirect (MAPK) targets of Nilotinib as well as the indirect (PRKC, MAPK, AKT, RPS6K) targets of Midostaurin, respectively. Moreover, our pipeline was able to characterize unexplored kinase-activities within the corresponding signaling networks. With our pipeline, we provide researchers and clinicians an instrument to monitor biological behavior of kinases in response or resistance to targeted treatment. Further investigations are warranted and ongoing to determine the utility of our pipeline to characterize mechanisms of disease progression and treatment failure.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-16_23:57:33.521.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Manfred Heller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-17 11:19:15	ID requested
⏵ 1	2022-02-16 23:57:34	announced

Hallal M, Braga-Lagache S, Jankovic J, Simillion C, Bruggmann R, Uldry AC, Allam R, Heller M, Bonadies N, Inference of kinase-signaling networks in human myeloid cell line models by Phosphoproteomics using kinase activity enrichment analysis (KAEA). BMC Cancer, 21(1):789(2021) [pubmed]

submitter keyword: phosphoproteomics, kinase activity, kinase-signaling network, myeloid malignancies

Nicolas Bonadies
contact affiliation	Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Switzerland Department for BioMedical Research (DBMR), University of Bern, Switzerland
contact email	nicolas.bonadies@insel.ch
lab head
Manfred Heller
contact affiliation	Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
contact email	pmscf@dbmr.unibe.ch
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/2021/09/PXD024806

PRIDE project URI

• PRIDE
  1. PXD024806
     1. Label: PRIDE project
     2. Name: Inference of Kinase-Signaling Networks in Human Myeloid Cell Line Models by Phosphoproteomics using Kinase Activity Enrichment Analysis (KAEA)