A gene encoding a 35-kilodalton guanosine triphosphate (GTP)-binding p
rotein, Gem, was cloned from mitogen-induced human peripheral blood T
cells. Gem and Rad, the product of a gene overexpressed in skeletal mu
scle in individuals with Type II diabetes, constitute a new family of
Ras-related GTP-binding proteins. The distinct structural features of
this family include the G3 GTP-binding motif, extensive amino- and car
boxyl-terminal extensions beyond the Ras-related domain, and a motif t
hat determines membrane association. Gem was transiently expressed in
human peripheral blood T cells in response to mitogenic stimulation; t
he protein was phosphorylated on tyrosine residues and localized to th
e cytosolic face of the plasma membrane. Deregulated Gem expression pr
evented proliferation of normal and transformed 3T3 cells. These resul
ts suggest that Gem is a regulatory protein, possibly participating in
receptor-mediated signal transduction at the plasma membrane.