Inserm U. 461, Récepteurs et signalisation des interleukines, faculté de pharmacie Paris-XI, 5, rue Jean-Baptiste-Clément, 92296 Châtenay-Malabry.
Rho family GTPases (Rho, Rac, Cdc42) act as molecular switches to control a large number of cellular functions, including actin cytoskeleton organization, cell cycle progression, apoptosis and gene regulation. The GDP/GTP cycling of Rho GTPases is controlled by exchange factors (GEF), GTPase activating proteins (GAP) and guanine dissociation inhibitors (GDI) and their cellular functions are mediated by effector proteins. Of the many actors in the Rho pathways some are mainly or exclusively expressed in the hematopoietic system and play specific roles: Rac2 controls the NADPH oxidase activation in phagocytes, the exchange factor Vav is critical for T lymphocyte activation and the Cdc42 effector WASP, when mutated leads to the Wiskott-Aldrich immunodeficiency. Finally, through their various effector pathways Rho GTPases participate in many of the specialized function of the immune system such as T lymphocyte proliferation and differentiation, antigen processing and presentation by dendritic cells, chemotaxis and T-cell mediated cytotoxicity.