ABSTRACT
The molecular mechanisms associated with the transduction of extracellular signals into intracellular messages frequently involve the guanine nucleotides, guanosine diphosphate (GDP) and guanosine triphosphate (GTP), as well as proteins that bind and hydrolyze GTP (GTPases), as essential components of biochemical pathways that may participate in the regulation of the adenylyl cyclase system, enzymes, or ion channels. A large family of GTP-binding proteins has been identified in eukaryotic cells. 1-10 This superfamily of GTP-binding proteins includes the high molecular weight heterotrimeric GTP-binding proteins involved in transmembrane signaling (G proteins), the 21-kDa (p21) Ras proteins encoded by ras proto-oncogenes, translation factors such as the eukaryotic elongation factors lα and 2 (EF-1α and EF-2), and monomeric low molecular weight GTP-binding proteins encoded by genes such as rab, rap, ral, rho, sec-4, and ypt-1. 11 Although these proteins have regions exhibiting high sequence similarity, they may be involved in different functions. However, the basic mechanism of the reactions catalyzed by GTP-binding proteins is similar and consists of the conversion of an inactive conformation bound to GDP to an active conformation bound to GTP, which is involved in signal transduction across the cell membrane. The active form is inactivated upon hydrolysis of bound GTP to bound GDP, which results in a shift of the tertiary structure of the protein. Conversion of the inactive to the active form of the protein by nucleotide exchange is regulated by an exchange-promoting protein (EPP), whereas the conversion of active (GTP-bound) to inactive (GDP-bound) is accelerated by a GTPase-activating protein (GAP), which stimulates intrinsic GTPase activity in the protein.
