Systems-wide Analysis of K-Ras, Cdc42, and PAK4 Signaling by Quantitative Phosphoproteomics

作者：Gnad Florian^*; Young Amy; Zhou Wei; Lyle Karen; Ong Christy C; Stokes Matthew P; Silva Jeffrey C; Belvin Marcia; Friedman Lori S; Koeppen Hartmut; Minden Audrey; Hoeflich Klaus P

来源：MOLECULAR & CELLULAR PROTEOMICS, 2013, 12(8): 2070-2080.

DOI：10.1074/mcp.M112.027052

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.

• 出版日期2013-8