title: Antibodies specific for amino acid 12 of the ras oncogene product inhibit GTP binding.
abstract: An antibody (anti-p21ser) was raised against a ras p21-related synthetic peptide and was able to recognize specifically the substitution of serine for glycine at amino acid 12 of p21. This substitution causes oncogenic activation of p21. Anti-p21ser was found to immunoprecipitate v-Ki-ras p21 and to strongly inhibit its ability to autophosphorylate and to bind GTP in an immunoabsorption assay. Furthermore, binding of the antibody to p21 was specifically inhibited by GTP or GDP, suggesting that amino acids around position 12 are part of the GTP/GDP binding site. These results, taken together with the observation that the microinjection of anti-p21ser into cells transformed by v-Ki-ras p21 causes a transient reversion of the cells to a normal phenotype [Feramisco, J. R., Clark, R., Wong, G., Arnheim, N., Milley, R. & McCormick, F. (1985) Nature (London) 314, 639-642], support the idea that interaction of p21 with guanine nucleotides is crucial to the transforming function of this protein.
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies; D002471:Cell Transformation, Neoplastic; D005998:Glycine; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D009857:Oncogenes; D010641:Phenotype; D016283:Proto-Oncogene Proteins p21(ras); D012694:Serine
chemical_list: D000906:Antibodies; D009363:Neoplasm Proteins; D012694:Serine; D006160:Guanosine Triphosphate; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D005998:Glycine