Small GTP-binding proteins

Five of the six loop regions (G1-G5 in Figure 13.4) that are present at the carboxy end of the p sheet in the Ras structure participate in the GTP binding site. Three of these loops, G1 (residues 10-17), G3 (57-60), and G4 (116-119), contain regions of amino acid sequence conserved among small GTP-binding proteins and the Ga subunits of trimerlc G proteins. 

The diversity of these subcellular actin structures is remarkable and appears to be determined by the interactions of many actin-binding proteins (ABPs) as well as by changes in the concentrations of intracellular signaling molecules such as Ca and cAMP, by small GTP-binding proteins, and by signals arising from mechanical stress. Approximately 50% of the actin molecules in most animal cells are unpolymerized subunits in the cytosolic pool and exist in a state of dynamic equilibrium with labile F-actin filamentous structures (i.e., new structures are formed while existing structures are renewed) (Hall, 1994). 

Hall, A. (1994). Small GTP-binding proteins and the regulation of the actin cytoskeleton. Ann. Rev. Cell Biol. 10,31-54. 

Ridley, A.J., Hall, A. (1992). The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70,389-399. 

COPI-coated vesicles mediate intra-Golgi transport and Golgi to ER retrograde transport. The coats of these vesicles do not show the geometric forms seen with clathrin coats and have a more complex protein composition [3]. Coat protein purification first lead to the identification of a complex composed of seven individual coat-protein subunits, known as COPI or coatomer. Some of these subunits bear a sequence similarity to clathrin adaptors. In addition, there is a small GTP-binding protein, Arfl, present on COPI-coated vesicles. 

SMALL GTP-BINDING PROTEINS (GTPases) MEDIATE CHANGES IN GENE EXPRESSION UPON NMDA RECEPTOR ACTIVATION 285... 

The discovery of PLCs reveals a fourth mechanism whereby the enzyme can be activated (Fig. 20-5). PLCs possesses two Ras-binding (RA) domains in its carboxyl terminal region, and occupancy of these by Ras-GTP results in activation of the enzyme. In addition, the enzyme possesses a CDC-25 domain at its N-terminus, which serves as a guanine nucleotide exchange factor (GEF) for small GTP-binding proteins such as Ras or RaplA. Thus PLCe can not only activate the GDP-bound forms of these small GTP-binding proteins but can also be... 

Eukaryotic cells utilize an efficient transport system that delivers macromolecules fast and secure to their destination. In the case of the small GTP binding proteins of the Ras family the modified C-terminus seems to be sufficient for addressing the polypeptide to its target membrane (in the case of Ras itself the plasma membrane). Lipopeptides with the C-terminal structure of N-Ras (either a pen-tamer with a C-terminal carboxymethylation and farnesylation or a heptapeptide with a palmitoyl thioester in addition) and a N-terminal 7-nitrobenz-2-oxa-l,3-diazolyl (NBD) fluorophore were microin-jected into NIH3T3 fibroblast cells and the distribution of the fluorophore was monitored by confocal laser fluorescence microscopy. Enrichment of the protein in the plasma membrane was efficient only for peptides with two hydrophobic modification sites, while the farnesylated but not palmitoylated peptide was distributed in the cytosol.1121... 

Abo, A., Pick, E., Hall, A., Totty, N., Teahan, C. G., Segal, A. W. (1991). Activation of the NADPH oxidase involves the small GTP-binding protein p2lmcl. Nature 353, 668-70. 

Table 6.1. Some small GTP-binding proteins of mammalian cells...

These latter observations suggest a role for arachidonic acid as a genuine second messenger, and further work is necessary to assess if such a role exists during neutrophil activation. It has also been proposed that arachidonic acid may dissociate p21rac and GDI ( 5.3.2.3), thus allowing the small GTP-binding protein to interact with pAl-phox and p66-phox in the assembly of active NADPH oxidase complexes. 

Downard, J. (1990). The ras superfamily of small GTP-binding proteins. TIBS 15, 467-72. 

Vargiu P, De Abajo R, Garcia-Ranea JA, Valencia A, Santisteban P, Crespo P, Bernal J (2004) The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors. Oncogene 23 559-568... 

Hall, A. The Cellular Function of Small GTP-Binding Proteins, Science, 635 (August 10. 1990). 

On astroglial cell lines (human astrocytoma ADF cells) low (nM) concentrations of the selective A3AR agonist Cl-IB-MECA induced a marked reorganization of cell cytoskeleton accompanied by induction of expression of small GTP-binding protein of the Rho family that is involved in control of actin cytoskeleton and by changes of intracellular distribution of the antiapoptotic protein Bcl-XL (Abbracchio et al. 1997, 2001). 

Spiliotis, M. and Brehm, K. (2004) Echinococcus multilocularis identification and molecular characterization of a Ral-like small GTP-binding protein. Experimental Parasitology 1 07, 1 63-1 72. 

Pasqualato, S., and Cherfils, J. (2005). Crystallographic evidence for substrate-assisted GTP hydrolysis by a small GTP binding protein. Structure 13, 533-540. 

Bhattacharya, M., Babwah, A. V., and Ferguson, S. S. (2004). Small GTP-binding protein-coupled receptors. Biochem. Soc. Trans. 32, 1040-1044. 

Arcaro, A. 1998. The small GTP-binding protein Rac promotes the dissociation of gelsolin from actin filaments in neutrophils. J Biol Chem. 273 805—13. 

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