A two-hit model for development of multiple endocrine neoplasia type 2B by RET mutations.
Biochem Biophys Res Commun
; 268(3): 804-8, 2000 Feb 24.
Article
en En
| MEDLINE
| ID: mdl-10679286
ABSTRACT
Multiple endocrine neoplasia (MEN) type 2B mutations have been reported at methionine 918 or alanine 883 in the tyrosine kinase domain of the RET proto-oncogene. Recently, a new combination of two germline missense mutations at valine 804 and tyrosine 806 was identified in a patient with MEN 2B-like clinical phenotypes including medullary thyroid carcinoma, mucosal neuroma, and marfanoid habitus. In this case, valine 804 and tyrosine 806 were replaced with methionine and cysteine, respectively. In the present study, biological activities of RET with these new mutations were compared with those with known MEN 2A or MEN 2B mutations. The transforming activity of RET with the V804M/Y806C mutation was about 8- to 13-fold higher than that of RET with a single V804M or Y806C mutation. Like RET with the M918T or A883F MEN 2B mutation, the transforming activity of RET with the V804M/Y806C mutation was not affected by substitution of phenylalanine for tyrosine 905 that abolished the activity of RET with the MEN 2A mutation. On the other hand, substitution of phenylalanine for tyrosines 864 and 952 drastically diminished the activity of RET with the V804M/Y806C, M918T or A883F mutation, suggesting that these three mutant proteins have similar biological properties.
Buscar en Google
Base de datos:
MEDLINE
Asunto principal:
Proto-Oncogenes
/
Proteínas Proto-Oncogénicas
/
Proteínas Tirosina Quinasas Receptoras
/
Mutación de Línea Germinal
/
Neoplasia Endocrina Múltiple Tipo 2b
/
Proteínas de Drosophila
/
Modelos Genéticos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2000
Tipo del documento:
Article
País de afiliación:
Japón