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Updated: Mar 21, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

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The small GTPases Ras and Rap1 bind to and control TORC2 activity

Ankita Khanna1, Pouya Lotfi2, Anita J Chavan2

  • 1Department of Cell Biochemistry, University of Groningen, Groningen, 9747AG, Netherlands.

Scientific Reports
|May 14, 2016
PubMed

Insights

Scientists identified Rap1 as a key regulator of Target of Rapamycin Complex 2 (TORC2) signaling. This discovery reveals how Rap1 and RasC pathways cooperate to control cell migration and TORC2 activity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Target of Rapamycin Complex 2 (TORC2) is crucial for cytoskeleton dynamics and cell migration, with implications in cancer metastasis.
  • Mechanisms governing TORC2 activity and function remain largely unelucidated.
  • In Dictyostelium, TORC2 regulates F-actin dynamics and cAMP production at the leading edge of migrating cells, downstream of RasC.

Purpose of the Study:

  • To identify novel regulators of TORC2 activity and function.
  • To elucidate the mechanism of TORC2 activation in directed cell migration.
  • To understand the interplay between Ras and Rap1 signaling pathways in controlling TORC2.

Main Methods:

  • Identification of binding partners for the TORC2 component RIP3/SIN1 using biochemical assays.
  • Investigation of the role of Rap1 in regulating TORC2 activity in response to RasC.
  • Analysis of the interaction between active RasC and the catalytic domain of TOR.

Main Results:

  • The small GTPase Rap1 was identified as a conserved binding partner of RIP3/SIN1.
  • Rap1 was found to positively regulate RasC-mediated activation of TORC2 in Dictyostelium.
  • Active RasC was shown to bind to the catalytic domain of TOR, suggesting a conserved activation mechanism.

Conclusions:

  • Rap1 is a novel regulator of TORC2, working in concert with RasC to control cell migration.
  • The findings suggest a mechanism for TORC2 activation involving direct binding of active RasC to the TOR catalytic domain.
  • Dual regulation by Ras and Rap1 allows for the integration of signaling pathways essential for directed cell migration.

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