Article

The RAF proteins take centre stage

Signal Transduction Team, Cancer Research UK Centre of Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
Nature Reviews Molecular Cell Biology (Impact Factor: 36.46). 12/2004; 5(11):875-85. DOI: 10.1038/nrm1498
Source: PubMed

ABSTRACT Since their discovery over 20 years ago, the RAF proteins have been intensely studied. For most of that time, the focus of the field has been the C-RAF isoform and its role as an effector of the RAS proteins. However, a report that implicates B-RAF in human cancer has highlighted the importance of all members of this protein kinase family and recent studies have uncovered intriguing new data relating to their complex regulation and biological functions.

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    • "By contrast, LS mutants behaved as loss-of-function mutations of SHP2, impairing ERK activation [10] [11] [12]. Within the heart, ERK1/2 are activated at the plasma membrane by Raf-1, followed by activation of small G protein Ras [13]. Harris et al. showed that dominant negative Raf-1 inhibited ERK1/2 activation in transgenic mice, which were resistant to hypertrophic stress but developed significant cardiomyocyte apoptosis [14]. "
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    • "pathway blocks the growth of melanoma cells harboring an oncogenic BRAF mutation and thus represents an attractive therapeutic target (Wellbrock et al., 2004; Miller and Mihm, 2006; Tsao et al., 2012). Oncogenic NRAS is capable of activating multiple downstream pathways, including BRAF- MEK-ERK, all of which are thought to play an important role in NRAS driven oncogenesis (Downward, 2003; Karnoub and Weinberg, 2008). "
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    • "The RAS-RAF-MEK-ERK signaling pathway is key for a variety of cellular functions including controlling cell proliferation and survival (Baccarini, 2005; Wellbrock et al., 2004). Dysregulation of this pathway is also important in cancer with most tumors exhibiting mutations in RAS and/or RAF (Brose et al., 2002). "
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