PXD007620-1

PXD007620 is an original dataset announced via ProteomeXchange.

Title	Specificity of phosphorylation responses to MAP kinase pathway inhibitors in melanoma cells, experiment 1 of 2
Description	We used phosphoproteomics to compare the responses of the ERK1/2 inhibitors, SCH772984 and GDC0994, and the MKK1/2 inhibitor, trametinib. These are compared with responses to the MKK1/2 inhibitor, selumetinib (AZD6244), previously measured by our lab in the same metastatic melanoma cell line. In three replicate experiments, we quantified a total of 12,805 class I phosphosites on 3,819 proteins in the trametinib-SCH772984-DMSO experiment, and 7,074 class I phosphosites on 2,453 in the GDC0994-SCH772984-DMSO experiment. This included 466 phosphosites that reproducibly decreased in response to at least one inhibitor in the trametinib-SCH772984-DMSO experiment and 414 phosphosites in the GDC0994-SCH772984-DMSO experiment. The results demonstrate linearity in signaling through the MAP kinase pathway. By comparing multiple inhibitors targeted to multiple tiers of protein kinases in the MAPK pathway, we gain insight into regulation and new targets of the oncogenic BRAF driver pathway in cancer cells, and a useful approach for evaluating the specificity of drugs and drug candidates. SILAC Experimental Design Experiment 1 Replicate 1: Heavy – DMSO, Medium – SCH772984, Light – Trametinib Replicate 2: Heavy – SCH772984, Medium – Trametinib, Light – DMSO Replicate 3: Heavy – Trametinib, Medium – DMSO, Light – SCH772984 SILAC Experimental Design Experiment 2 Replicate 1: Heavy – DMSO, Medium – SCH772984, Light – GDC0994 Replicate 2: Heavy – SCH772984, Medium – GDC0994, Light – DMSO Replicate 3: Heavy – GDC0994, Medium – DMSO, Light – SCH772984 File List 1. Zipped MaxQuant search results folder containing index and output folders for each raw file, ‘combined’ output folder, and mqpar.xml MaxQuant search parameters file 2. Individual raw files of phosphopeptide-enriched ERLIC fractions and total protein fractions 3. Zipped MaxQuant version used for analysis 4. FASTA file containing Uniprot human identifications 5. Instructions for viewing annotated spectra
HostingRepository	PRIDE
AnnounceDate	2018-01-02
AnnouncementXML	Submission_2018-01-02_02:18:44.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joel Basken
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-01 02:02:21	ID requested
⏵ 1	2018-01-02 02:18:45	announced
2	2024-10-22 04:41:01	announced	2024-10-22: Updated project metadata.

Basken J, Stuart SA, Kavran AJ, Lee T, Ebmeier CC, Old WM, Ahn NG, Specificity of Phosphorylation Responses to Mitogen Activated Protein (MAP) Kinase Pathway Inhibitors in Melanoma Cells. Mol Cell Proteomics, 17(4):550-564(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, Melanoma, SILAC, trametinib, selumetinib, SCH772984, GDC0994

Natalie G. Ahn
contact affiliation	Department of Chemistry and Biochemistry. University of Colorado, Boulder. Boulder, CO 80303
contact email	natalie.ahn@colorado.edu
lab head
Joel Basken
contact affiliation	University of Colorado - Boulder
contact email	joel.basken@colorado.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007620
     1. Label: PRIDE project
     2. Name: Specificity of phosphorylation responses to MAP kinase pathway inhibitors in melanoma cells, experiment 1 of 2