title: Ras nanoclusters: a new drug target?
abstract: Ras proteins on the plasma membrane are laterally segregated into transient nanoclusters that are essential for high-fidelity signal transmission by the Ras/MAPK cascade. The dynamics of Ras nanocluster assembly and disassembly control MAPK signal output. BRaf inhibitors paradoxically activate CRaf and MAPK signaling in Ras-transformed cells. In our recent study, we showed that BRaf inhibition significantly enhances nanoclustering of oncogenic K- and N-Ras, but not H-Ras by increasing the frequency of Ras nanocluster formation. This disrupted spatiotemporal dynamics of Ras nanocluster fully accounts for the observed effects of Raf inhibitors on Ras signal transmission. Here together with other studies, we propose that the dynamics of Ras nanoclusters may represent a novel target for future therapeutic intervention.
authors: Department of Integrative Biology and Pharmacology, The University of Texas Medical School, Houston, Houston, TX, USA.
authors: Kwang-Jin
authors: KJ
authors: Cho
authors: John F
authors: JF
authors: Hancock
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins
keywords: BRaf inhibitors; nanocluster; pharmacological target; plasma membrane; ras proteins