title: Target of rapamycin (TOR) kinase in Trypanosoma brucei: an extended family.
abstract: The complex life cycle of Trypanosoma brucei provides an excellent model system to understand signalling pathways that regulate development. We described previously the classical functions of TOR (target of rapamycin) 1 and TOR2 in T. brucei. In a more recent study, we described a novel TOR kinase, named TOR4, which regulates differentiation from the proliferative infective form to the quiescent form. In contrast with TOR1 loss-of-function, down-regulation of TOR4 triggers an irreversible differentiation process through the development of the insect pre-adapted quiescent form. TOR4 governs a signalling pathway distinct from those controlled by the conventional TOR complexes TORC1 and TORC2. Depletion of TOR4 induces all well-known characteristics of the quiescent developmental stage in trypanosomes, including expression of the PAD (proteins associated with differentiation) surface proteins and transcriptional down-regulation of the VSG (variant surface glycoprotein) gene. TOR4 kinase forms a structurally and functionally distinct complex named TORC4. TOR4 associates with LST8 (lethal with sec-13 protein 8) and other factors including an armadillo-domain-containing protein and the major vault protein, which probably serves as a scaffold for this kinase. Research in T. brucei, a protozoan parasite that diverged from the eukaryotic tree early in evolution, may help to uncover new functions of TOR kinases.
authors.affiliation: Consejo Superior de Investigaciones Cientificas, IPBLN, 18100 Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Saldivia
authors.forename: Antonio
authors.initials: A
authors.lastname: Barquilla
authors.forename: Jean-Mathieu
authors.initials: JM
authors.lastname: Bart
authors.forename: Rosario
authors.initials: R
authors.lastname: Diaz-González
authors.forename: Michael N
authors.initials: MN
authors.lastname: Hall
authors.forename: Miguel
authors.initials: M
authors.lastname: Navarro
mesh_terms: D000818:Animals; D008018:Life Cycle Stages; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000502:physiology
chemical_list: D058570:TOR Serine-Threonine Kinases