Gene interactions and pathways from curated databases and text-mining
Mol Immunol 2009, PMID: 19586661

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

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

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.

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Text Mining Data

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

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

TORC1 → Hsp90: " Pharmacologic inhibition of Hsp90 leads to a decrease in raptor expression and TORC1 activity "

raptor → Hsp90: " Pharmacologic inhibition of Hsp90 leads to a decrease in raptor expression and TORC1 activity "

Manually curated Databases

No curated data.