RESUMEN
The rfp/ret transforming gene was generated by DNA rearrangement which occurred during transfection of NIH 3T3 cells. The amino-terminal half of Rfp with a RING finger motif was fused to the truncated Ret receptor tyrosine kinase, leading to a transforming sequence, Rfp/Ret. In the present study, to elucidate the importance of a RING finger motif for its transforming activity, we mutated cysteine or histidine residues present in the motif that are believed to be crucial for the tertiary structure of the protein. Substitution of Cys-16, Cys-31, or His-33 markedly decreased the transforming activity of Rfp/Ret. These mutations also resulted in a striking decrease of tyrosine phosphorylation of the mutant proteins in transfectants. In contrast, mutations of Cys-118 or His-124 in the second cysteine/histidine-rich motif (called B box) of Rfp/Ret did not affect its activity. These results thus indicated that the RING finger structure is critical for the full transforming activity of Rfp/Ret.
Asunto(s)
Proteínas de Unión al ADN , Proteínas de Drosophila , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Células 3T3 , Animales , Línea Celular Transformada , ADN Complementario , Ratones , Mutagénesis , Proteínas Nucleares/genética , Fosforilación , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ret , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Recombinantes de Fusión/genética , Transfección , Tirosina/metabolismo , Ubiquitina-Proteína LigasasRESUMEN
Nine cases of amyloidosis involving the gastrointestinal tract were reviewed for the presence of abnormal gastrointestinal gas by taking plain roentgenograms of the abdomen (PRA) as a diagnostic adjunct. Findings were compared to data obtained by conventional barium study or endoscopic examination. PRA revealed marked gaseous dilatation of the gastrointestinal tract simulating intestinal obstruction in three cases and a moderate or mild increase of gas in two cases each. Abnormality was thus found in seven of the nine cases by PRA. Conventional barium study by means of upper gastrointestinal series, small bowel series and barium enema showed abnormal findings in five of seven cases. Endoscopic examination of the stomach and distal colon disclosed mucosal abnormality in three of seven cases. The rate of abnormal findings detected by the three methods cannot easily be compared to each other because of the differences in symptoms and treatment of individual patients. Nevertheless, PRA seem to be valuable in demonstrating a high rate of abnormalities in amyloidosis.