The TC21 oncoprotein interacts with the Ral 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. cDNA clones encoding the carboxy-terminal region of the RalGDS protein were isolated from human B-cell and HeLa cDNA libraries. RalGDS is an exchange factor that stimulates GDP dissociation from Ral, another member 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 participate in cross-talking between Ral and TC21 signalling pathways.
López-Barahona
M
M
Department of Molecular Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Bustelo
X R
XR
Barbacid
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D015723:Gene Library; D011905:Genes, ras; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D020725:ral GTP-Binding Proteins
D008565:Membrane Proteins; D011994:Recombinant Proteins; D006160:Guanosine Triphosphate; C087360:RRAS2 protein, human; C490200:Rras2 protein, mouse; D019204:GTP-Binding Proteins; D020559:Monomeric GTP-Binding Proteins; D020725:ral GTP-Binding Proteins