La proteína MAP4K3 participa, a través de mecanismos independientes, en la regulación independientes, en la regulación de las rutas de señalización TOR y JNK

Resumen

SUMMARYThe formation of organs with a characteristic pattern, size and form requires a strict genetic control of cellular growth, cell proliferation, cell differentiation and cell death. Drosophila melanogaster is a convenient model system to analyze gene function during development, because it allows to manipulate gene activity and to assign specific functions to the relevant genes. Our main objective was to identify the signaling pathways affected by the gene CG7097 (happyhour) during the development of the Drosophila wing. CG7097 encodes the Drosophila orthologous of the MAP4K3 protein, a conserved Ser/Thr kinase of the Ste20 kinase superfamily. Using loss-of-function mutants and over-expression conditions of the gene we find that MAP4K3 levels affect cell growth and viability. These requirements are related to the modulation of the TORC1 and JNK signalling pathways by MAP4K3, and are best detected when the larvae grow in a medium with low protein concentration or are exposed to irradiation. We also find that MAP4K3 display strong genetic interactions with different components of the InR/TOR signalling pathway, and can interact directly with the GTPases RagA and RagC and with the multi-domain kinase Tor. We suggest that MAP4K3 has two independent functions during wing development, one related to the activation of the JNK pathway in response to stress and other in the assembling or activation of the TORC1 complex, being critical to modulate cellular responses to changes in nutrient availability.