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Related Experiment Videos

TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function.

Stefanie S Schalm1, Diane C Fingar, David M Sabatini

  • 1The Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Current Biology : CB
|May 16, 2003
PubMed
Summary

The TOR signaling (TOS) motif in 4E-BP1 acts as a docking site for the mTOR/raptor complex, facilitating cell growth regulation. This motif is crucial for 4E-BP1 phosphorylation and its release from eIF4E, impacting cell size.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mammalian target of rapamycin (mTOR) regulates cell growth and proliferation.
  • mTOR signaling involves translation regulators eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1).
  • A TOR signaling (TOS) motif in 4E-BP1 and S6K1 was identified, but its mechanism in mediating mTOR signaling was unclear.

Purpose of the Study:

  • To elucidate the role of the TOS motif in 4E-BP1 in mediating mTOR signaling.
  • To investigate how the TOS motif facilitates mTOR-dependent regulation of cell growth.

Main Methods:

  • Investigated 4E-BP1 binding to raptor, an mTOR-interacting protein.
  • Assessed in vitro and in vivo phosphorylation of 4E-BP1 by the mTOR/raptor complex.

Related Experiment Videos

  • Utilized overexpression of a mutant 4E-BP1 (F114A) with a modified TOS motif to study cell size regulation.

    • Main Results:

    • A functional TOS motif in 4E-BP1 is essential for its binding to raptor.
    • The TOS motif is required for efficient in vitro and in vivo phosphorylation of 4E-BP1 by the mTOR/raptor complex.
    • mTOR/raptor-regulated phosphorylation of 4E-BP1 is necessary for its release from eIF4E, and a mutated TOS motif reduces cell size.

    Conclusions:

    • The TOS motif serves as a docking site for the mTOR/raptor complex.
    • This interaction is critical for multisite phosphorylation of 4E-BP1.
    • The TOS motif-mediated process regulates eIF4E release and is essential for mTOR-dependent cell growth.