Signal transduction GTPases

G proteins comprise several families of diverse cellular proteins that subserve an equally diverse array of cellular functions. These proteins derive their name from the fact that they bind the guanine nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP) and possess intrinsic GTPase activity. G proteins play a central role in signal transduction as well as in a myriad of cellular processes, including membrane vesicle transport,... 

The family of eukaryotic Ras-like small GTPases may be divided into subfamilies, namely those of ARF, Rab, Ran, Ras, Rho, and Sar (ARF, RAB, RHO, RAS, RHO, SAR), which all contain representatives from fungi, plants, and metazoa. Consequently, these subfamilies and their cellular functions are likely to have emerged early in eukaryotic history. This implies that the last common ancestor of fungi, plants, and metazoa possessed vesicular transport (ARF and Sar), membrane trafficking (Rab), nuclear transport (Ran), signal transduction (Ras), and regulation of the actin cytoskeleton (Rho) functions. 

LT Escherichia coli (ETEC) ABs GTPases Heterotrimeric Altered signal transduction Severe diarrhea... 

PT Bordetella pertussis AB4 GTPases Heterotrimeric Altered signal transduction Pertussis (whooping cough)... 

Ras Signal transduction factors Monomeric G-protein with very low GTPase activity, which maintains the protein in the active state. 

The termination of signal transduction results from the hydrolysis of GTP to GDP by GTPase thereby returning the G-protein to its inactive form. 

The most important components of intracellular signal transduction are the protein kinases, protein phosphatases, regulatory GTPases and adapter proteins ... 

Signal transduction between Ras protein and Raf kinase is based on a specific interaction of the two proteins, which can only be performed by the activated, GTP-bound form of Ras protein. The inactive, GDP-form of Ras protein shows significantly weaker binding to Raf kinase (Herrmann et al., 1995). Complex formation is not linked to stimulation of GTPase activity of Ras protein, and thus it is assumed that termination of signal transduction only occins on dissociation of Raf kinase or hydrolysis of the boimd GTP. The lifetime of the GTP state is determined by the GTPase activity of the Ras protein, which itself is subject to regulation by GAP proteins. 

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