Genetic and biochemical dissection of the S6K signaling pathway in Drosophila melanogaster. T.A. Radimerski ¹, J. Montagne ¹, F. Rintelen ², H. Stocker ², E. Hafen ², G. Thomas ¹. 1) Dept Growth Control, Friedrich Miescher Inst, Basel Stadt, Switzerland; 2) Zoology Institute, University Of Zurich, Switzerland.

   Homozygous ds6k null mutants show a strong developmental delay and an overall reduction in body size due to smaller cells but not less cells (Montagne et. al, 1999. Science 285:2126). From studies in mammalian systems it is established that S6K resides on the insulin/InR/PI3K pathway. Furthermore, S6K activation is dependent on amino acid levels via TOR (Target Of Rapamycin) signaling. However, mutants in chico, Dp110, Dakt1, dTOR and dS6K display growth-related but distinct phenotypes (Oldham et. al, 2000. Genes Dev. 14:2689; and unpublished data). Here we set out to determine which signaling molecules in the InR pathway are required for DS6K activation employing a number of different approaches; (i) genetic interactions in the dorsal compartment of the wing, (ii) DS6K activity in larvae of different signaling component mutants and (iii) DS6K activation in Drosophilacell culture lines after depletion of potential upstream signaling elements using dsRNAi. Our data suggest that DS6K activation is independent of Chico and Dakt1, but requires Dp110, PDK1 and dTOR signaling inputs.