Interactions between Ras and Raf: key regulatory proteins in cellular transformation

Molecular Reproduction and Development
M Marshall

Abstract

Ras proteins function during cell growth and development as essential, plasma membrane-bound signaling proteins. Current evidence suggests that Ras is part of a signal transduction chain extending from extracellular signals to transcriptional regulation in the nucleus. Growth factor and cytokine activation of many tyrosine kinase and kinase-linked receptors recruits many proteins to the plasma membrane including Ras-specific guanine nucleotide releasing proteins (GNRP). Under the influence of a GNRP, Ras proteins bind GTP, resulting in activation of the Ras signal. The GTP-bound form of Ras is capable of interacting directly with RasGAP, neurofibromin, and the Raf kinases. Although believed to be endowed with some signaling capacity, RasGAP and neurofibromin act primarily to negatively regulate Ras. Based upon genetic and biochemical studies in a variety of diverse organisms, the Raf kinases are considered the primary targets of Ras signaling. Activation of the Raf kinases is the first step in a cascade of multiple protein kinases, including Mek, Erk1, and Erk2. We are attempting to understand structurally how activated Ras proteins interact specifically with Raf kinases to induce the downstream signals necessary for cell divis...Continue Reading

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