Abstract
Ras proteins activate cytoplasmic signaling cascades that mediate responses in growth, cellular differentiation, and survival. Therefore, it is not surprising that mutationally activated Ras proteins have been found in many human cancers. Determining the effector protein signaling pathways through which Ras causes cellular transformation is important for creating targeted therapeutics that will specifically block the oncogenic effects of activated Ras. In 1993, Raf serine/threonine kinases were identified as key downstream effectors of Ras signaling and transformation. While Raf remains the best characterized Ras effector, the rapid expansion of the Ras effector pool has demonstrated that Ras transforming activity is also mediated by Raf-independent effector signaling pathways. These include phosphatidylinositol 3-kinase and phospholipase regulators of phospholipid metabolism, and guanine nucleotide exchange factors and activators of Ras-related proteins. Further complexity arose when a new and seemingly incongruous group of pro-apoptotic Ras effectors with tumor suppressor function was identified. This chapter will summarize recent findings of mutational activation of B-Raf in human cancers and examine the importance of non-Raf effectors in Ras-mediated signaling and transformation
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Chenette, E.J., Repasky, G.A., Der, C.J. (2006). Effectors of Ras-Mediated Oncogenesis. In: Der, C. (eds) RAS Family GTPases. Proteins and Cell Regulation, vol 4. Springer, Dordrecht. https://doi.org/10.1007/1-4020-4708-8_6
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