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Kinase Activities Associated with mTOR

  • Chapter
TOR

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 279))

Abstract

Although mTOR is a member of the PI-kinase-related kinase family, mTOR possesses serine-threonine protein kinase activities, which phosphorylate itself and exogenous substrates. mTOR autophosphorylates in vitro and is phosphorylated in vivo on serine residues. Ser2481, which is located in a His-Ser-Phe motif near the conserved car boxyl- terminal mTOR tail, has been reported as an autophosphorylation site in vivo and in vitro. The significance of the autophosphorylation remains unclear. Another phosphorylation site on mTOR in vivo is Ser2448. This site appears not to be an autophosphorylation site but a site potentially phosphorylated by protein kinase B (PKB). mTOR immunopurified from culture cells or tissues phosphorylates in vitro p70 S6 kinase (p70) α and p70β, mainly on Thr412 or Thr401, respectively, located in a Phe-Thr-Tyr motif. Another exogenous substrate phosphorylated by immunopurified mTOR in vitro is eIF4E-binding protein 1 (4E-BP1) at sites corresponding to those phosphorylated in vivo during insulin stimulation in a Ser/Thr-Pro motif. Recently, raptor, a 150-kDa TOR-binding protein that contains a carboxyl-terminal WD-repeat domain, was discovered as a scaffold for the mTOR-catalyzed phosphorylation of 4E- BP1 and for the mTOR-mediated phosphorylation and activation of p70α. Other potential substrates phosphorylated by mTOR are nPKCδ, nPKCε:, STAT3, and p53. The requirement of raptor for binding to and phosphorylation by mTOR of these potential substrates would clarify their physiological importance in the mTOR signaling pathway.

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Authors and Affiliations

  1. Biosignal Research Center, Kobe University, 657-8501, Kobe, Japan

    K. Yonezawa, K.-I. Yoshino, C. Tokunaga & K. Hara

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  1. K. Yonezawa
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  2. K.-I. Yoshino
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  3. C. Tokunaga
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  4. K. Hara
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Editors and Affiliations

  1. Friedrich-Miescher-Institute, Maulbeerstrasse 66, 4058, Basel, Switzerland

    George Thomas

  2. Whitehead Institute, 9 Cambridge Center, Cambridge, MA, 02142, USA

    David M. Sabatini MD, PhD

  3. Biozentrum, University of Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland

    Michael N. Hall

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Yonezawa, K., Yoshino, KI., Tokunaga, C., Hara, K. (2004). Kinase Activities Associated with mTOR. In: Thomas, G., Sabatini, D.M., Hall, M.N. (eds) TOR. Current Topics in Microbiology and Immunology, vol 279. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18930-2_16

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  • DOI: https://doi.org/10.1007/978-3-642-18930-2_16

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