G protein Pathways and Regulation of Neoplastic Transformation

Abstract

The processes that underlie the conversion of a normal cell to a transformed phenotype are complex. Signal transduction pathways are thought to play important roles in regulating events that eventually result in the transformed phenotype. It is now well established that many oncogenes code for mutated proteins whose normal counterparts are components of cellular signaling systems (1). Cooperation between such oncogenes in regulating transformation is a well-established phenomenon (2). In normal physiological state signal transduction pathways are important for regulating cellular functions so that they are responsive to current environmental conditions. All cells possess several signaling pathways that are used to convey a variety of signals. Pathways that involve tyrosine kinases are used to produce long term responses such as regulation of proliferation. Many of the best known oncogenes such as v-erb-B, v-src, v-ras and v-raf are components of the tyrosine kinase signaling pathway. Other pathways, such as those that utilize heterotrimeric G protein as signal transducers, are largely used to evoke acute responses such as the activities of metabolic enzymes. Often cells receive multiple signals that simultaneously activate different signaling pathways.