Drosophila target of rapamycin kinase functions as a multimer

Yong Zhang, Charles J. Billington, Duojia Pan, Thomas P. Neufeld

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Target of rapamycin (TOR) is a conserved regulator of cell growth and metabolism that integrates energy, growth factor, and nutrient signals. The 280-kDa TOR protein functions as the catalytic component of two large multiprotein complexes and consists of an N-terminal HEAT-repeat domain and a C-terminal Ser/Thr kinase domain. Here we describe an allelic series of mutations in the Drosophila Tor gene and show that combinations of mutations in the HEAT and kinase domains of TOR display the rare genetic phenomenon of intragenic complementation, in which two or more defective proteins assemble to form a functional multimer. We present biochemical evidence that TOR self-associates in vivo and show that this multimerization is unaffected by positive or negative signals upstream of TOR. Consistent with multimerization of TOR, recessive mutations in the HEAT and kinase domains can dominantly interfere with wild-type TOR function in cells lacking TSC1 or TSC2. TOR multimerization thus partially accounts for the high apparent molecular weight of TOR complexes and offers novel therapeutic strategies for pathologies stemming from TOR hyperactivity.

Original languageEnglish (US)
Pages (from-to)355-362
Number of pages8
JournalGenetics
Volume172
Issue number1
DOIs
StatePublished - Jan 1 2006

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Sirolimus
Drosophila
Phosphotransferases
Mutation
TOR Serine-Threonine Kinases
Genetic Phenomena
Multiprotein Complexes
Terminal Repeat Sequences
Energy Metabolism
Intercellular Signaling Peptides and Proteins
Molecular Weight
Pathology
Food
Growth

ASJC Scopus subject areas

  • Genetics

Cite this

Drosophila target of rapamycin kinase functions as a multimer. / Zhang, Yong; Billington, Charles J.; Pan, Duojia; Neufeld, Thomas P.

In: Genetics, Vol. 172, No. 1, 01.01.2006, p. 355-362.

Research output: Contribution to journalArticle

Zhang, Y, Billington, CJ, Pan, D & Neufeld, TP 2006, 'Drosophila target of rapamycin kinase functions as a multimer', Genetics, vol. 172, no. 1, pp. 355-362. https://doi.org/10.1534/genetics.105.051979
Zhang, Yong ; Billington, Charles J. ; Pan, Duojia ; Neufeld, Thomas P. / Drosophila target of rapamycin kinase functions as a multimer. In: Genetics. 2006 ; Vol. 172, No. 1. pp. 355-362.
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