THE TC21 ONCOPROTEIN INTERACTS WITH THE RAT GUANOSINE NUCLEOTIDE DISSOCIATION FACTOR

TC21 is a highly oncogenic member of the Ras superfamily of small GTP binding proteins. We have used the yeast two hybrid system to identify proteins that interact with an oncogenic form of the TC21 protein. cD NA clones encoding the carboxy-terminal region of the RalGDS protein w ere isolated from human B-cell and HeLa cDNA libraries. RalGDS is an e xchange factor that stimulates GDP dissociation from Ral, another memb er of the Ras superfamily of proteins. The interaction between RalGDS to TC21 is direct and appears to be mediated by the effector domain of TC21 and the carboxy-terminal region of RalGDS. Moreover, RalGDS only binds to TC21 in its active, GTP-loaded configuration. These results suggest that RalGDS might be an effector molecule for TC21 and may par ticipate in cross-talking between Ral and TC21 signalling pathways.