and RAD, the product of a gene overexpressed in skeletal muscle and in individuals with type II diabetes mellitus, constitute a new family of RAS-related GTP-binding proteins. The distinct structural features of this family include the GTP-binding motif, extensive amino- and carboxyl-terminal extensions beyond the RAS-related domain, and a motif that determines membrane association. GEM was transiently expressed in human peripheral blood T cells in response to mitogen stimulation; the protein was phosphorylated on tyrosine residues and localized to the cytosolic face of the plasma membrane. Deregulated GEM expression prevented proliferation of normal and transformed NIH 3T3 cells. These results suggested that GEM is a regulatory protein, possibly participating in receptor-mediated signal transduction at the plasma membrane.