Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation

Greg M. Delgoffe, Thomas P. Kole, Robert J. Cotter, Jonathan D. Powell

Research output: Contribution to journalArticle

Abstract

The mammalian target of rapamycin (mTOR) is an evolutionarily conserved kinase which plays a role in integrating environmental cues. mTOR signals via two complexes: TORC1, which contains the Regulatory Associated Protein of TOR (raptor), and TORC2, which contains the Rapamycin-insensitive Companion of TOR (rictor). The immunosuppressive/anti-cancer agent rapamycin inhibits TORC1 function by disrupting the mTOR-raptor interaction. In an effort to understand the downstream consequences of TORC1 activation in T cells we performed a proteomic analysis of raptor binding proteins. Using this approach we have identified Hsp90 as an activation-induced binding partner of raptor in T cells. Pharmacologic inhibition of Hsp90 leads to a decrease in raptor expression and TORC1 activity. Furthermore, full T cell activation during Hsp90 blockade leads to T cell tolerance in the form of anergy. Overall, our findings suggest that Hsp90 inhibitors might represent a novel means of promoting T cell tolerance.

Original languageEnglish (US)
Pages (from-to)2694-2698
Number of pages5
JournalMolecular Immunology
Volume46
Issue number13
DOIs
StatePublished - Aug 1 2009

Keywords

  • Anergy
  • Hsp90
  • Rapamycin
  • Raptor
  • T cell
  • mTOR

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation'. Together they form a unique fingerprint.

  • Cite this