Asunto(s)
Western Blotting/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Animales , Anticuerpos , Especificidad de Anticuerpos , Humanos , Mutación , Proteínas Nucleares/inmunología , Nucleofosmina , ConejosAsunto(s)
Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 5/genética , Regulación Leucémica de la Expresión Génica , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/genética , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Enfermedad Aguda , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Humanos , Proteínas Nucleares/biosíntesis , Nucleofosmina , Proteínas de Fusión Oncogénica/análisis , Proteínas de Fusión Oncogénica/biosíntesis , Fracciones Subcelulares/química , Translocación Genética/genéticaRESUMEN
Shc proteins are targets of activated tyrosine kinases and have been implicated in the transmission of activation signals to Ras. Upon phosphorylation, Shc proteins form stable complexes with cellular tyrosine-phosphorylated proteins and with the Grb2 adaptor protein. Two Shc isoforms of 52 and 46 kDa have been characterized. They share a C-terminal SH2 domain, a proline- and glycine-rich region (collagen homologous region 1; CH1) and a N-terminal phospho-tyrosine binding domain (PTB). We report her ethe initial characterization of two Shc related human cDNAs: ShcB and ShcC. The ShcB and ShcC cDNAs code for proteins that are highly similar and share the same modular organization as Shc. PTB and SH2 domains of ShcB and ShcC have similar binding specificities in vitro and bind to activated EGFR in a phosphotyrosine-dependent manner. Based on these findings we propose to rename Shc as ShcA. Anti-ShcB and anti-ShcC antibodies recognize specific polypeptides of 52, 47 kDa (ShcB) and 54 kDa (ShcC) in mammalian cells. Since these two genes are predominantly expressed in specific brain tissues, these Shc family members may be involved in cell type-specific signaling, in the nervous system.