RESUMEN

Toll receptors transduce signals that activate Rel-family transcription factors, such as NF-κB, by directing proteolytic degradation of inhibitor proteins. In mammals, the IκB Kinase (IKK) phosphorylates the inhibitor IκBα. A ßTrCP protein binds to phosphorylated IκBα, triggering ubiquitination and proteasome mediated degradation. In Drosophila, Toll signaling directs Cactus degradation via a sequence motif that is highly similar to that in IκBα, but without involvement of IKK. Here we show that Pelle, the homolog of a mammalian regulator of IKK, acts as a Cactus kinase. We further find that the fly ßTrCP protein Slimb is required in cultured cells to mediate Cactus degradation. These findings enable us for the first time to trace an uninterrupted pathway from the cell surface to the nucleus for Drosophila Toll signaling.

Asunto(s)

Proteínas de Drosophila/metabolismo , Drosophila/enzimología , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/fisiología , Secuencia de Aminoácidos , Animales , Proteínas de Ciclo Celular/metabolismo , Proteínas de Drosophila/genética , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Modelos Biológicos , Datos de Secuencia Molecular , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Proteolisis , Receptores Toll-Like/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo