Diagram of daf-2/IGFR signaling pathway and tyrosine metabolic pathway.

(A) For dauer formation in C. elegans the daf-2/IGFR receptor lies upstream of a PI3 kinase signaling cascade consisting of age-1/PI3 kinase, the phosphoinoside-dependent kinase pdk-1, and the protein kinase B family kinases akt-1 and akt-2. Both AKT-1 and AKT-2 act to phosphorylate DAF-16/FOXO and prevent entry of this protein into the nucleus. Inhibition of AKT-1 leads to entry of DAF-16/FOXO into the nucleus without the activation of DAF-16 target genes. This suggested that other pathways acted to control the transcriptional activity of nuclear DAF-16/FOXO. The eak genes are a group of structurally unrelated genes which act in a cell non-autonomous manner to restrain the transcriptional activity of nuclear DAF-16/FOXO through an undefined molecular mechanism. (B) Tyrosine is degraded to fumarate and acetoacetate via a five step degradation pathway. Shown are the names and structures of the intermediates as well as the names of the enzymes which catalyze each step. Also shown are mutant alleles affecting enzymes in the pathway that are studied in this work.



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