RESUMEN
Rap1 and Rap2 are similar Ras-like G proteins but perform distinct functions. By the affinity chromatography/mass-spectrometry approach and the yeast two-hybrid screening, we identified Misshapen/NIKs-related kinase (MINK) as a novel Rap2-interacting protein that does not interact with Rap1 or Ras. MINK is a member of the STE20 group of mitogen-activated protein kinase kinase kinase kinases. The interaction between MINK and Rap2 was GTP-dependent and required Phe39 within the effector region of Rap2; the corresponding residue in Rap1 and Ras is Ser. MINK was enriched in the brain, and both MINK and its close relative, Traf2- and Nck-interacting kinase (TNIK), interacted with a postsynaptic scaffold protein containing tetratricopeptide repeats, ankyrin repeats and a coiled-coil region (TANC1) and induced its phosphorylation, under control of Rap2 in cultured cells. These are novel actions of MINK and TNIK, and consistent with a role of MINK as a Rap2 effector in the brain.
Asunto(s)
Encéfalo/metabolismo , Venenos de Crotálidos/metabolismo , Lectinas Tipo C/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Unión al GTP rap/metabolismo , Secuencia de Aminoácidos , Animales , Emparejamiento Cromosómico , Venenos de Crotálidos/genética , Quinasas del Centro Germinal , Humanos , Lectinas Tipo C/genética , Ratones , Datos de Secuencia Molecular , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , RatasRESUMEN
Metastatic male occult HER2-positive breast cancer can be successfully treated with trastuzumab monotherapy.