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Ras-GTP dimers activate the Mitogen-Activated Protein Kinase (MAPK) pathway

2015; National Academy of Sciences; Volume: 112; Issue: 26 Linguagem: Inglês

10.1073/pnas.1509123112

1091-6490

Xiaolin Nan, Tanja Tamgüney, Eric A. Collisson, Li-Jung Lin, Cameron Pitt, Jacqueline Galeas, Sophia Lewis, Joe W. Gray, Frank McCormick, Steven Chu,

Protein Kinase Regulation and GTPase Signaling

Significance Rat sarcoma (Ras) proteins play central roles in both normal and oncogenic signaling. Mechanisms of how Ras interacts with its effectors on the cell membrane, however, are still poorly understood, significantly hampering efforts to target this molecule in human cancer. Here we have used quantitative superresolution fluorescence microscopy in combination with carefully engineered biological systems to show that Ras dimers drive oncogenic signaling through the Raf-MAPK pathway. Our study suggests a new, dimer model of Ras-Raf signaling and the potential value of Ras dimers as a therapeutic target.