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Small G proteins are monomeric G proteins with molecular weight of 20-40 kDa. Like heterotrimeric G proteins, their activity depends on the binding of GTP. More than 100 small G proteins have been identified. They are classified into five families: Ras, Rho, Rab, Ran and Arf (Table).
Figure 6-E-3. Cycling of the Ras protein between active and inactive states. Like other G proteins, Ras can switch between GTP-bound and GDP-bound states. Transition from the GDP-bound to the GTP-bound state is catalyzed by guanine nucleotide exchange factor (GEF) which induces exchange between the bound GDP and the cellular GTP. The reverse transition is catalyzed by a GTPase-activating protein (GAP) which induces hydrolysis of the bound GTP.
Ras and cancer Mutations of the Ras proto-oncogenes (H-Ras, N-Ras, K-Ras) are found in about 25% of all human tumors. Most of these mutations result in the abrogation of the normal GTPase activity of Ras. The Ras mutants can still bind to GAP, but cannot catalyze GTP hydrolysis. As a result, they remain in the active state for a much longer period. Malignant transformation may arise from the unregulated stimulation of Ras signaling pathways, which either stimulate cell growth (reference) or inhibit apoptosis (reference).
Review Articles: Physiological role of ROCKs in the cardiovascular system - Am J Physiol Cell Physiol, 2006. Rho Kinases in Cardiovascular Physiology and Pathophysiology - Circulation Research, 2006. Rho-Kinase Is an Important Therapeutic Target in Cardiovascular Medicine - Arterio. Thromb. and Vascular Biology. 2005. Rho GTPases, Statins, and Nitric Oxide - Circulation Research, 2005. Raf kinase as a target for anticancer therapeutics - Mol. Cancer Ther. 2005. Role of the Ras-Association Domain Family 1 Tumor Suppressor Gene in Human Cancers - Cancer Research, 2005. The love�hate relationship between Ras and Notch - Genes and Development, 2005. Multiple roles of Rap1 in hematopoietic cells: complementary versus antagonistic functions - Blood, 2005. PAK and other Rho-associated kinases - Biochem. J., 2005. Structural Clues to Rab GTPase Functional Diversity - J. Biol. Chem., 2005. Ras, Akt, and Mechanotransduction in the Cardiac Myocyte - Circulation Research, 2003. Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy - Blood, 2003. Farnesyltransferase Inhibitors - Cancer Research, 2003. Small GTP-Binding Proteins - Physiological Reviews, 2001. Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? - Blood, 2000. Guanine nucleotide exchange factors for Rho GTPases: turning on the switch - Genes and Development, 2002.
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