Proteomics

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Oncogenic pathways in uveal melanoma identified by phosphoproteomic analysis


ABSTRACT: The uveal melanoma cell lines MP41 and MP46 driven by oncogenic G11 (Q209L) and Gq (Q209L), respectively, and a control cell line OCM-1A driven by oncogenic BRAF (V600E) were treated for 24 hours with FR900359, a highly specific inhibitor of Gq/11. Protein extracts were collected and TMT labeled prior to LC-MS analysis. The enrichment of phosphopeptides from fractions of each sample was performed using IMAC prior to LC-MS. Proteomic and phospho-proteomic data analyses were performed to identify changes in post-translational modification in signaling pathways regulated by Gq/11 in these cells.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Kendall J. Blumer  

PROVIDER: MSV000090700 | MassIVE | Fri Nov 11 09:31:00 GMT 2022

SECONDARY ACCESSION(S): PXD038115

REPOSITORIES: MassIVE

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Publications

Protein Kinase Signaling Networks Driven by Oncogenic Gq/11 in Uveal Melanoma Identified by Phosphoproteomic and Bioinformatic Analyses.

Onken Michael D MD   Erdmann-Gilmore Petra P   Zhang Qiang Q   Thapa Kisan K   King Emily E   Kaltenbronn Kevin M KM   Noda Sarah E SE   Makepeace Carol M CM   Goldfarb Dennis D   Babur Özgün Ö   Townsend R Reid RR   Blumer Kendall J KJ  

Molecular & cellular proteomics : MCP 20230919 11


Metastatic uveal melanoma (UM) patients typically survive only 2 to 3 years because effective therapy does not yet exist. Here, to facilitate the discovery of therapeutic targets in UM, we have identified protein kinase signaling mechanisms elicited by the drivers in 90% of UM tumors: mutant constitutively active G protein α-subunits encoded by GNAQ (Gq) or GNA11 (G11). We used the highly specific Gq/11 inhibitor FR900359 (FR) to elucidate signaling networks that drive proliferation, metabolic r  ...[more]

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