| First Author | Delgoffe GM | Year | 2009 |
| Journal | Mol Immunol | Volume | 46 |
| Issue | 13 | Pages | 2694-8 |
| PubMed ID | 19586661 | Mgi Jnum | J:151711 |
| Mgi Id | MGI:4355100 | Doi | 10.1016/j.molimm.2009.05.185 |
| Citation | Delgoffe GM, et al. (2009) Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation. Mol Immunol 46(13):2694-8 |
| abstractText | 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. |
