ABSTRACT
The rac gene family consisting of racl and rac2 is the latest member of the ras superfamily of GTP-binding proteins. Products of the rac family, like those of the rho genes, undergo ADP-ribosylation by botulinum C3 ADP-ribosyltransferase (C3 exoenzyme). Hence the name rac is derived (ras-related C3 botulinum toxin substrate). Among the ras superfamily, the primary structure of rac is most related to those of CDC42 and rho. To date, the rac family has been studied only in human tissues and cells of human origin, and its phylogenic distribution has not been reported. Human rac genes, particularly rac2, are expressed extensively in cells of myeloid origin, suggesting that they may not be a housekeeping gene but play specific roles in special types of cells. A rac gene product was purified partially only from human platelets and its biochemical properties are not known in detail. Its cellular functions have also not been clarified yet. Botulinum C3 exoenzyme has been used to analyze functions of the ADP-ribosylation substrates, rho and rac proteins, in the cell. This ADP-ribosylation occurs at an asparagine residue (Asn 41 ) in the putative effector domain of a rho protein. The rac proteins have an asparagine residue at the corresponding position and are presumed to be ADP-ribosylated there. C3 exoenzyme incubated with or microinjected into cultured cells causes ADP-ribosylation of cellular substrates and evokes several phenotypic changes in the cells. These studies have suggested that rho and/or rac proteins are involved in cytoskeletal organization and may have some interaction with a membrane receptor. However, none of these studies was carried out in cells with identified ADP-ribosylation substrates, which makes it difficult to attribute specific roles to each species of rho and rac proteins. Future studies with C3 exoenzyme will be carried out in defined systems and clarify physiological functions for each member of the ADP-ribosylation substrates. Phylogeny of rac genes will be revealed and their actions will also be analyzed in more simple systems like yeast.
