Rac1 Regulates the Activity of mTORC1 and mTORC2 and Controls Cellular Size Academic Article uri icon

Overview

MeSH Major

  • Cell Size
  • Multiprotein Complexes
  • Neuropeptides
  • Proteins
  • TOR Serine-Threonine Kinases
  • rac GTP-Binding Proteins

abstract

  • Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two separate complexes, mTORC1 and mTORC2, that function to control cell size and growth in response to growth factors, nutrients, and cellular energy levels. Low molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 complex, but regulation of mTORC2 is poorly understood. Here, we report that Rac1, a member of the Rho family of GTPases, is a critical regulator of both mTORC1 and mTORC2 in response to growth-factor stimulation. Deletion of Rac1 in primary cells using an inducible-Cre/Lox approach inhibits basal and growth-factor activation of both mTORC1 and mTORC2. Rac1 appears to bind directly to mTOR and to mediate mTORC1 and mTORC2 localization at specific membranes. Binding of Rac1 to mTOR does not depend on the GTP-bound state of Rac1, but on the integrity of its C-terminal domain. This function of Rac1 provides a means to regulate mTORC1 and mTORC2 simultaneously.

publication date

  • April 8, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3750737

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2011.03.017

PubMed ID

  • 21474067

Additional Document Info

start page

  • 50

end page

  • 61

volume

  • 42

number

  • 1