Cells respond in many ways to environmental changes including altering gene expression, physically moving locations, changes to cell-cell interactions, differentiation and even altering their life spans. This is achieved through a signalling network that consists of several signalling pathways. The network receives multiple signals, interprets the signals, amplified and then transmits the signals. One of the best characterised signalling pathways involves the ras GTPase family. The importance of this family of small GTPases to human health was first recognised through the identification of the human H-Ras, N-Ras and K-Ras genes as being oncogenic.
The RGK subfamily of small GTPases which includes REM1, GEM, RRAD and REM2 are characterised by sequence changes in the functionally important switch I loop and the G3 (DXXG) motif. These changes result in significant decrease in enzymatic turnover effectively making these proteins GTP binding proteins rather than catalytic enzymes. The significance from a functional point of view is that these proteins are likely to be always in the active state.
The family also has N- and C-terminal extensions that contain Ser/Thr residues that after phosphorylation form a complex with 14-3-3 proteins with a subsequent increase in GEM protein half life (Ward et al, 2004). Calmodulin, a protein important in calcium regulation, is also able to bind to GEM (Fisher et al, 1996). This interaction is linked to one of REM's cellular functions which is the regulation of calcium channel activity through the beta subunit interaction (Beguin et al, 2006; Finlin et al, 2003).
REM1 has been localised to endothelial cells where it controls the morphology of these cells by the development of long cytoplasmic extensions and reorganistion of the actin cytoplasm (Pan et al 2000).
