Proteomics

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A phosphoproteomic comparison of B-RAFV600E and MKK1/2 inhibitors in melanoma cells, part 1


ABSTRACT: To provide insight into the molecular nature of the clinical responses seen with MAPK pathway inhibition in melanoma, we used quantitative mass spectrometry to characterize the inhibitor-dependent phosphoproteome of human melanoma cells treated with the B-RAFV600E inhibitor PLX4032 (vemurafenib) and the MKK1/2 inhibitor AZD6244 (selumetinib).. In three replicate experiments, we quantified a total of 23,986 phosphosites on 4,722 proteins. This included 1,317 phosphosites that reproducibly decreased in response to at least one inhibitor.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Melanocyte

DISEASE(S): Melanoma

SUBMITTER: Scott Stuart  

LAB HEAD: Natalie G. Ahn

PROVIDER: PXD001560 | Pride | 2016-02-25

REPOSITORIES: Pride

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A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells.

Stuart Scott A SA   Houel Stephane S   Lee Thomas T   Wang Nan N   Old William M WM   Ahn Natalie G NG  

Molecular & cellular proteomics : MCP 20150407 6


Inhibitors of oncogenic B-RAF(V600E) and MKK1/2 have yielded remarkable responses in B-RAF(V600E)-positive melanoma patients. However, the efficacy of these inhibitors is limited by the inevitable onset of resistance. Despite the fact that these inhibitors target the same pathway, combination treatment with B-RAF(V600E) and MKK1/2 inhibitors has been shown to improve both response rates and progression-free survival in B-RAF(V600E) melanoma patients. To provide insight into the molecular nature  ...[more]

Publication: 1/2

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