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

Mol Cell Proteomics. 2013 Aug;12(8):2070-80. doi: 10.1074/mcp.M112.027052. Epub 2013 Apr 22.


Although K-Ras, Cdc42, and PAK4 signaling are commonly deregulated in cancer, only a few studies have sought to comprehensively examine the spectrum of phosphorylation-mediated signaling downstream of each of these key signaling nodes. In this study, we completed a label-free quantitative analysis of oncogenic K-Ras, activated Cdc42, and PAK4-mediated phosphorylation signaling, and report relative quantitation of 2152 phosphorylated peptides on 1062 proteins. We define the overlap in phosphopeptides regulated by K-Ras, Cdc42, and PAK4, and find that perturbation of these signaling components affects phosphoproteins associated with microtubule depolymerization, cytoskeletal organization, and the cell cycle. These findings provide a resource for future studies to characterize novel targets of oncogenic K-Ras signaling and validate biomarkers of PAK4 inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Mice
  • NIH 3T3 Cells
  • Phosphopeptides / metabolism
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Proteomics
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Signal Transduction
  • cdc42 GTP-Binding Protein / metabolism*
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*


  • Cdc42 protein, mouse
  • Phosphopeptides
  • Phosphoproteins
  • Pak4 protein, mouse
  • p21-Activated Kinases
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)
  • cdc42 GTP-Binding Protein