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Sci. Signal., 29 June 2010
Vol. 3, Issue 128, p. ra49
[DOI: 10.1126/scisignal.2000803]


Evolution of the TSC1/TSC2-TOR Signaling Pathway

Jaco Serfontein1, R. Ellen R. Nisbet2*, Christopher J. Howe2{dagger}{ddagger}, and Petrus J. de Vries3,4{dagger}

1 Cambridgeshire and Peterborough NHS Foundation Trust, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK.
2 Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
3 Neurodevelopmental Service, Cambridgeshire and Peterborough NHS Foundation Trust, Peterborough PE3 6DB, UK.
4 Developmental Psychiatry Section, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge CB2 8AH, UK.

* Present address: Sansom Institute for Health Research, University of South Australia, North Terrace, Adelaide, South Australia 5000, Australia.

{dagger} These authors contributed equally to this work.

Abstract: The TSC1/TSC2-TOR signaling pathway [the signaling pathway that includes the heterodimeric TSC1 (tuberous sclerosis 1 protein)–TSC2 (tuberous sclerosis 2 protein) complex and TOR (target of rapamycin)] regulates various cellular processes, including protein synthesis, in response to growth factors and nutrient availability. Homologs of some pathway components have been reported from animals, fungi, plants, and protozoa. These observations led to the perception that the whole pathway is evolutionarily conserved throughout eukaryotes. Using complete genome sequences, we show that, contrary to this view, the pathway was built up from a simpler one, present in the ancestral eukaryote, coupling cell growth to energy supplies. Additional elements, such as TSC1 and TSC2, were "bolted on" in particular eukaryotic lineages. Our results also suggest that unikonts [Opisthokonta (including animals and fungi) and Amoebozoa] form a monophyletic group with the Excavata and Chromalveolata. A previous proposal, that the root of the eukaryotic "tree of life" lies between the unikonts and other organisms, should therefore be reevaluated.

{ddagger} To whom correspondence should be addressed. E-mail: c.j.howe{at}

Citation: J. Serfontein, R. E. R. Nisbet, C. J. Howe, P. J. de Vries, Evolution of the TSC1/TSC2-TOR Signaling Pathway. Sci. Signal. 3, ra49 (2010).

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