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The B-Raf kinase is an important molecule in cell signaling that functions as a Ras pathway effector to initiate ERK activation and is mutationally activated in numerous human cancers and in certain developmental disorders. Ritt et al. (p. 806-819) now show that normal as well as mutant B-Raf proteins are targets of a feedback phosphorylation/dephosphorylation cycle that regulates both Ras binding and B-Raf/C-Raf heterodimerization. Strikingly, perturbations in this cycle are found to modulate the signaling potential of B-Raf, suggesting that targeting the regulatory machinery that controls this cycle may prove useful in treating certain diseases with constitutive B-Raf signaling.
The cytokine interleukin-7 (IL-7), required for the survival of pro-T cells and mature T cells, was previously shown to regulate Bcl-2 family members Bax, Bad, and Bcl-2. A study by Li et al. (p. 590-600) now shows that the BH3-only protein Bim is critical for killing mature T cells with an effector memory phenotype following IL-7 deprivation but plays a redundant role in the apoptosis of pro-T cells during thymic development. IL-7 withdrawal decreases Mcl-1 levels, releasing free Bim, and induces serine phosphorylation of Bim, which enhances its proapoptotic activity.