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Systems-wide analysis of K-Ras, Cdc42, and PAK4 signaling by quantitative phosphoproteomics

Florian Gnad1, Amy Young, Wei Zhou

  • 1Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, California 94080, USA. gnadf@gene.com

Molecular & Cellular Proteomics : MCP
|April 24, 2013
PubMed

Insights

This study maps cancer-related K-Ras, Cdc42, and PAK4 signaling pathways. It identifies 2152 phosphoproteins involved in cell cycle and cytoskeletal organization, offering new targets for cancer research.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • K-Ras, Cdc42, and PAK4 signaling pathways are frequently altered in cancer.
  • Comprehensive analysis of downstream phosphorylation events is limited.

Purpose of the Study:

  • To quantitatively analyze phosphorylation signaling downstream of K-Ras, Cdc42, and PAK4.
  • To identify overlapping signaling networks and affected cellular processes.

Main Methods:

  • Label-free quantitative proteomics was employed.
  • Analysis focused on phosphopeptides and their regulated proteins.

Main Results:

  • Quantified 2152 phosphorylated peptides across 1062 proteins.
  • Defined overlap in phosphopeptides regulated by K-Ras, Cdc42, and PAK4.
  • Identified affected phosphoproteins involved in microtubule depolymerization, cytoskeletal organization, and cell cycle.

Conclusions:

  • Provides a comprehensive resource for K-Ras signaling research.
  • Identifies potential biomarkers for PAK4 inhibition therapies.
  • Highlights the interconnectedness of these signaling pathways in cancer.

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