title: Systems-wide analysis of K-Ras, Cdc42, and PAK4 signaling by quantitative phosphoproteomics.
abstract: 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.
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, California 94080, USA. gnadf@gene.com
authors.forename: Florian
authors.initials: F
authors.lastname: Gnad
authors.forename: Amy
authors.initials: A
authors.lastname: Young
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Karen
authors.initials: K
authors.lastname: Lyle
authors.forename: Christy C
authors.initials: CC
authors.lastname: Ong
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Stokes
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Silva
authors.forename: Marcia
authors.initials: M
authors.lastname: Belvin
authors.forename: Lori S
authors.initials: LS
authors.lastname: Friedman
authors.forename: Hartmut
authors.initials: H
authors.lastname: Koeppen
authors.forename: Audrey
authors.initials: A
authors.lastname: Minden
authors.forename: Klaus P
authors.initials: KP
authors.lastname: Hoeflich
mesh_terms: D000818:Animals; D051379:Mice; D041681:NIH 3T3 Cells; D010748:Phosphopeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D040901:Proteomics; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C581598:Cdc42 protein, mouse; D010748:Phosphopeptides; D010750:Phosphoproteins; C492065:Pak4 protein, mouse; D054462:p21-Activated Kinases; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras); D020764:cdc42 GTP-Binding Protein