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

Greg M. Delgoffe, Thomas P. Kole, Robert J. Cotter, Jonathan 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 2009

Fingerprint

Sirolimus
T-Lymphocytes
Proteins
Immunosuppressive Agents
Protein Binding
Proteomics
Cues
Carrier Proteins
Phosphotransferases
mechanistic target of rapamycin complex 1
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation. / Delgoffe, Greg M.; Kole, Thomas P.; Cotter, Robert J.; Powell, Jonathan.

In: Molecular Immunology, Vol. 46, No. 13, 08.2009, p. 2694-2698.

Research output: Contribution to journalArticle

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