Human GTP binding protein RAD

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.

Rad (Ras like GTPase associated with Diabetes) is a typical member of the RGK family that includes Gem/ Kir, Rem, and Rem2. Members of the Rad family of GTPases possess unique features in comparison to Ras superfamily, containing major N and C terminal extensions, lack of the typical prenylation motifs and unconserved aminoacid changes in the Guanine nucleotide binding domain. These changes result in significant decrease in enzymatic turnover effectively making these proteins GTP binding proteins rather than catalytic enzymes.

Rad is overexpressed in a number of normal and pathological conditions. It is expressed primarily in skeletal and cardiac muscle and was increased an average of 8.6-fold in the muscle of Type II diabetics as compared to normal individuals (Reynet and Kahn, 1993). Rad is also up-regulated in regenerating limb muscle of the newt (Shimizu-Nishikawa et al, 2001), in human breast cancers (Tseng et al, 2001), and in human peripheral blood mononuclear cells in response to acute heat shock (Sonna et al, 2002).