Signal transduction small GTPases

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. 

Cholera toxin interferes with the function of a key G-protein in the small intestine by deactivating its intrinsic GTPase activity. The consequence is uncontrolled activation of the signal transduction pathway which produces the second messenger 3, 5 -cyclic AMP leading to a life-threatening diarrhea following the activation of ion and water secretion. 

Small G-proteins (20-25 kDa), which belong to the Ras superfamily of small GTPases. These proteins are homologous to the alpha (a) subunit found in heterotrimers, and are in fact monomeric. However, they also bind GTP and GDP and are involved in signal transduction. 

Figure 9-1 Signal transduction cascades involved in cell migration. Cell migration is regulated by various molecules, such as small GTPases, kinases, phosphatases, and other molecules (ellipses) which regulate actin dynamics in response to extraceUnlar stimuli.

Figure 9-3 Structures of compounds that affect Rho-family GTPases and downstream signal transductions. Molecules in parentheses are targets of small molecules.

---