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Oncogenic Ras forms nanoclusters and promotes Raf dimerization, activation, and signaling in the mitogen-activated protein kinase (MAPK) pathway (Raf/MEK/ERK). In the cytosol, Raf is autoinhibited, but the high-affinity Ras–(RBD) Ras-binding domain interaction releases the autoinhibition. Raf is activated through side-by-side dimerization. Rap1 dilutes oncogenic Ras nanoclusters, suppressing Raf’s activation. Abbreviations: CRD, cysteine-rich domain; KD, kinase domain.
