PXD019005-2

PXD019005 is an original dataset announced via ProteomeXchange.

Title	Kinome profiling: cabozantinib treatment in a mouse model of plexiform neurofibroma
Description	Neurofibromatosis type 1 (NF1) is the most common autosomal dominant disorder, affecting 1 in 3,500 individuals worldwide and predisposing to cancer. Germline mutations in the NF1 gene, encoding the p21Ras GTPase-activating protein (GAP) neurofibromin, are the underlying cause for NF1. Somatic inactivation of the wild type copy of NF1 leads to deregulated Ras signaling. Clinical manifestations are diverse for NF1 patients, but the predominant lesions are plexiform neurofibroma (PNF), arising from the Schwann cell (SC) lineage. While PNF are generally benign, approximately 10% of patients will experience PN progression to highly aggressive malignant peripheral nerve sheath tumors (MPNST) with poor prognosis. There are currently no approved targeted therapies for PNF or MPNST. In this study, we used a conditional mouse model of NF1, test the multi-receptor tyrosine kinase inhibitor, cabozantinib (XL184). Mice were treated with vehicle or with cabozantinib for 3 or 7 days. Tissue was harvested, lysates prepared, and the lysate was used for kinome profiling. From cell lines or tumor tissue, protein lysates are prepared and passed over an affinity matrix consisting of Sepharose beads covalently coupled to a mixture of linker-adapted Type I kinase inhibitors. Kinase capture is reproducible and is a function of affinity for kinases for the immobilized inhibitors, expression level of the kinase, as well as the activation state of the kinase. Following affinity purification, kinases are identified and their multiplexed kinase inhibitor bead binding quantified by mass spectrometry (MIB/MS). Our goal is to identify the kinome changes in NF1 plexiform neurofibroma induced by cabozantinib treatment.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:48:12.306.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Steven Angus
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-06 01:10:29	ID requested
1	2023-05-18 08:37:27	announced
⏵ 2	2023-11-14 08:48:15	announced	2023-11-14: Updated project metadata.

Fisher MJ, Shih CS, Rhodes SD, Armstrong AE, Wolters PL, Dombi E, Zhang C, Angus SP, Johnson GL, Packer RJ, Allen JC, Ullrich NJ, Goldman S, Gutmann DH, Plotkin SR, Rosser T, Robertson KA, Widemann BC, Smith AE, Bessler WK, He Y, Park SJ, Mund JA, Jiang L, Bijangi-Vishehsaraei K, Robinson CT, Cutter GR, Korf BR, Blakeley JO, Clapp DW, Shih CS, Armstrong AE, Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial. Nat Med, 27(1):165-173(2021) [pubmed]

submitter keyword: receptor tyrosine kinase,NF1, XL184

Gary L. Johnson
contact affiliation	Department of Pharmacology University of North Carolina - Chapel Hill Chapel Hill, NC 27599
contact email	gary_johnson@med.unc.edu
lab head
Steven Angus
contact affiliation	Indiana University School of Medicine
contact email	sangus@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019005
     1. Label: PRIDE project
     2. Name: Kinome profiling: cabozantinib treatment in a mouse model of plexiform neurofibroma