Small G-protein networks: their crosstalk and signal cascades.

Small GTP-binding proteins (G-proteins) exist in eukaryotes from yeast to human and constitute a superfamily consisting of more than 100 members. This superfamily is structurally classified into at least five families: the Ras, Rho/Rac/Cdc42, Rab, Sar1/Arf, and Ran families. They play key roles not only in temporal but also in spatial determination of specific cell functions. It has become clear that multiple small G-proteins form signalling cascades that are involved in various cellular functions, such as budding processes of the yeast and regulation of the actin cytoskeleton in fibroblasts. In addition, two distinct small G-proteins regulate specific cellular functions in a cooperative or antagonistic manner. A single small G-protein exerts various biological responses through different downstream effectors. Moreover, some of these downstream effectors sequentially activate further downstream effector proteins. Thus, small G-proteins appear to exert their functions through their mutual crosstalk and multiple downstream effectors in a variety of cellular functions.