GDP/GTP exchange proteins for small GTP-binding proteins

Small GTP-binding proteins (G proteins) have GDP-bound inactive and GTP-bound active forms which are interconvertible by GDP/GTP exchange and GTPase reactions. The former reaction is regulated by GDP/GTP exchange proteins (GEPs), and the latter reaction is catalyzed by small G proteins by themselves and is regulated by GTPase-activating and -inhibiting proteins (GAPs and GIPs, respectively; Figure 1). The rate-limiting step for the GDP/GTP exchange reaction is the dissociation of GDP from small G proteins. Since the intracellular concentration of GTP is much higher than that of GDP, once GDP dissociates from small G proteins, GTP is associated with the guanine nucleotide-free form of small G proteins. Two types of GEPs have been identified: one is a stimulatory type, named GDP dissociation stimulator (GDS), and the other is an inhibitory type, named GDP dissociation inhibitor (GDI). GDS stimulates the dissociation of GDP from and thereby the subsequent binding of GTP to each small G protein, whereas GDI inhibits the dissociation of GDP from and thereby, the subsequent binding of GTP to each small G protein. GDS has been found for ras p21, smg p21 (identical to the rapi protein), and rho p21, and GDI has been found for smg p25A (identical to the rab3A protein) and rho p21. Among these regulatory proteins, smg p21 GDS and smg p25A GDI have been most extensively investigated. In this article, we mainly review these two regulatory proteins and briefly ras p21 GDS, rho p21 GDS, and rho p21 GDI.