title: Evolution of the TOR pathway.
abstract: The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and provide a practical framework on which experimental evidence can be compared between species. Here we performed phylogenetic analyses on the components of the TOR pathway and determined their point of invention. We find that the two TOR complexes and a large part of the TOR pathway originated before the Last Eukaryotic Common Ancestor and form a core to which new inputs have been added during animal evolution. In addition, we provide insight into how duplications and sub-functionalization of the S6K, RSK, SGK and PKB kinases shaped the complexity of the TOR pathway. In yeast we identify novel AGC kinases that are orthologous to the S6 kinase. These results demonstrate how a vital signaling pathway can be both highly conserved and flexible in eukaryotes.
authors: Theoretical Biology and Bioinformatics, Department of Biology, Science Faculty, Utrecht University, Padualaan 8, Utrecht, The Netherlands. Teunis.J.P.vanDam@gmail.com
authors: Teunis J P
authors: TJ
authors: van Dam
authors: Fried J T
authors: FJ
authors: Zwartkruis
authors: Johannes L
authors: JL
authors: Bos
authors: Berend
authors: B
authors: Snel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D020440:Gene Duplication; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008957:Models, Genetic; D046912:Multiprotein Complexes / Q000235:genetics; D010802:Phylogeny; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D046912:Multiprotein Complexes; D015800:Protozoan Proteins; D014157:Transcription Factors; D058570:TOR Serine-Threonine Kinases