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. Author manuscript; available in PMC: 2011 Sep 22.
Published in final edited form as: Nature. 2010 Mar 18;464(7287):427–430. doi: 10.1038/nature08902

Figure 4. MEK/ERK induction occurs via transactivation of RAF dimers.

Figure 4

a, Similarly to RAF inhibitors, JAB34 inhibits MEK/ERK at higher concentrations. 293H cells expressing V5-tagged catC or catCS428C were treated with either vehicle or 10μM JAB34 for 1 hour. b, Coexpression of drug-sensitive V5-tagged catC with drug-resistant FLAG-catC reveals that activation in the homodimer occurs in trans. 293H cells expressing the indicated mutants V5-tagged catC and FLAG-tagged catC were treated with a dose of JAB34 (10μM/1 hour) that inhibits catCS428C when expressed alone. c, Activation in the context of the heterodimer BRAF/CRAF occurs in trans. 293H cells co-expressing FLAG-tagged wild-type BRAF and V5- tagged kinase-dead catC (catCD486N) (lanes 3,4) or JAB34-sensitive/kinase-dead catC (catCS428C/D486N) (lanes 5,6) treated with vehicle or 10μM JAB34 for 1 hour. d, HT-29 cells (colorectal – BRAFV600E) were transfected with EGFP or HA-tagged N-RASG12V and treated with PLX4720 (1μM/1hour). Lysates were blotted for pMEK and pERK.