[PDF][PDF] Rho family members: activators of MAP kinase cascades

AB Vojtek, JA Cooper - Cell, 1995 - core.ac.uk
AB Vojtek, JA Cooper
Cell, 1995core.ac.uk
Low molecularweight GTP-binding proteins are molecular switches that control a diverse
array of biological processes (Bourne et al., 1991). When bound to GTP, these proteins
transduce signals to effector proteins. When bound to GDP, these proteins are in an inactive
state. The cycling between the active, GTP-bound state and the inactive, GDP-bound state is
controlled by positive and negative modulators that directly contact the GTP-binding protein.
Positive modulators, guanine nucleotide dissociation stimulators (GDSs), catalyze the …
Low molecularweight GTP-binding proteins are molecular switches that control a diverse array of biological processes (Bourne et al., 1991). When bound to GTP, these proteins transduce signals to effector proteins. When bound to GDP, these proteins are in an inactive state. The cycling between the active, GTP-bound state and the inactive, GDP-bound state is controlled by positive and negative modulators that directly contact the GTP-binding protein. Positive modulators, guanine nucleotide dissociation stimulators (GDSs), catalyze the dissociation of GDP. Subsequently, GTP binds, and the protein is active. Negative modulators, GTPase-activating proteins (GAPS), stimulate the intrinsic GTP hydrolytic activity of the GTP-binding proteins and, hence, the formation of the inactive, GDP-bound state.
Approximately 50 low molecular weight GTPases have been described (Chardin, 1991). The family members can be subdivided, on the basis of sequence homology, into five classes: Ras, Rab, Arf, Ran, and Rho. Ras family members (H-Ras, K-Ras, N-Ras, R-Ras, TC21, RaplAl Rap1 B, and RapPAIRapPB) play salient roles in cell growth and development. The members of the Rab/Arf subfamilies monitor and direct the movements of vesicles within the cell. Ran is required for nuclear protein import. And, finally, the Rho family members (Cdc42/G25K, Racl, Rac2, RhoA, RhoB, and RhoC) play dynamic roles in the regulation of the actin cytoskeleton. Regulated changes in the actin cytoskeleton are required for cytokinesis, for cell motility, for vesicle trafficking, for pinocytosis, and, in the yeast Saccharomyces cerevisiae, for bud site selection and for polarized cell growth. Each of the small GTPases of the Rho subfamily participates in distinct patterns of actin reorganization. Rat is required for membrane ruffling, whereas Rho is required for the formation of stress fibers (Ridley and Hall, 1992; Ridley et al., 1992). Cdc42 was first identified in the yeast S. cerevisiae, where it is required for polarized cell growth (Adamset al., 1990); subsequently, a homolog of this yeast protein, Cdc42Hs (G25K), was identified from mammalian cells, where it regulates the formation of actin-containing microspikes, called filopodia (Kozma et al., 1995; Nobes and Hall, 1995).
core.ac.uk