Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2016 Sep 6;2:16028. doi: 10.1038/celldisc.2016.28

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

Copyright © 2016 The Author(s)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

PMC Copyright notice

Proteomic analysis of the global signaling state of melanoma cells with RTK-resistance mechanism reveals extensive alterations in cell attachment and cytoskeleton-related signaling processes. (a) Global phospho-profiling of two parental (P)/resistant (R) cell line pairs of the RTK-resistance mechanism (M229P/R and M238P/R; vem=6 h treatment with 1 μm vemurafenib/PLX4032 (vem)). Each column of the heatmap represents a phospho-peptide. The fold change of phosphorylation compared with the respective parental cell line is color coded in shades of red (upregulated in resistant cells) or green (downregulated in resistant cells). The phospho-profile was generated with a quantitative, label-free mass-spectrometry technique established in our laboratory [38]. (b) Significantly altered phosphorylation sites show same trend in both cell line pairs. A highly significant association between the direction of change for the M229 and M238 pair is observed (Fisher’s exact test; P-value <2.2×10⁻¹⁶). See Supplementary Figure S3 for more details. (c) Illustrative functional protein network of differentially regulated phospho-proteins highlights the observed alterations in cytoskeleton and cell attachment processes in RTK-resistance mechanism cells. The node core and border color shows phosphorylation and gene expression regulation (see legend; darker shades indicate stronger deregulation; missing values are gray). Gene expression data are from Nazarian et al. ([9]; geometric mean of fold changes for M238R/P and M229R/P). The network was generated with the Reactome FI plugin in Cytoscape [94]. The Reactome FI database combines curated interactions from Reactome and other pathway databases with statistically filtered uncurated pairwise relationships from various sources including protein interaction and gene co-expression data sets. Phospho-proteins significantly altered in RTK-resistance mechanism supplemented with differentially regulated genes were linked by functional interactions from the Reactome FI database (network edges). The clusters were identified manually, guided by computational analysis [95].