FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2533981475> ?p ?o ?g. }

• W2533981475 abstract "Abstract Full T cell activation requires antigen recognition (Signal 1) in the context of costimulation (Signal 2). Our group and others have determined that the mammalian Target of Rapamycin (mTOR) plays an important role in integrating costimulatory signals. Specifically, Th1 T cell activation in the absence of mTOR activation leads to tolerance in the form of T cell anergy. mTOR is an evolutionarily-conserved serine/threonine kinase which has been shown to interpret environmental cues in mammalian cells. mTOR is activated by an array of diverse inputs including insulin, amino acids, growth factors and CD28. mTOR signals through two signaling complexes: TORC1 and TORC2. A critical component of TORC1 signaling is the Regulatory Associated Protein of TOR (raptor). One of the central questions in understanding mTOR function is determining how diverse upstream signals can lead to diverse downstream functional consequences. To address this issue in T cells we undertook a proteomic approach to identify novel binding proteins for raptor. Jurkat T cells were either incubated in serum-free media or hyper-activated. Raptor was immunoprecipitated (IP) from the two lysates, separated by SDS-PAGE and silver stained. Next, protein bands that were differentially bound to raptor in the lysates from stimulated versus unstimulated cells were identified. One band located near 90 kDa was excised and using mass spectrometry subsequently determined to be Hsp90, a chaperone protein necessary for the correct folding of many protein “clients”. These findings were next confirmed in primary T cells. Upon activation with anti-CD3 and anti-CD28, IP of raptor led to co-IP of Hsp90 and IP of Hsp90 led to the concomitant precipitation of raptor. To further determine the role of the Hsp90-raptor interaction in T cells we used 17-AAG, an Hsp90 inhibitor. Primary T cells were stimulated in the presence of rapamycin or 17-AAG. Incubation with 17-AAG but not rapamycin led to a decrease in raptor protein levels consistent with the concept that raptor is an Hsp90 client. Functionally, this led to a decrease in TORC1 activation as measured by phosphorylation of S6K-1. More importantly, although17-AAG did not inhibit IL-2 production upon initial stimulation, primary T cells stimulated with anti-CD3 and anti-CD28 in the presence of 17-AAG failed to produce IL-2 upon rechallenge 5 days later; they were anergic. Overall, our findings demonstrate a novel activation-induced interaction between Hsp90 and raptor in T cells. This interaction can regulate the decision between TCR-induced activation and tolerance. Hsp90 inhibitors are currently being evaluated as anti-neoplastic agents, and while such agents do not acutely inhibit T cell function, they may induce anergy in activated Th1 cells. Thus, Hsp90 inhibitors might be incorporated into novel immunosuppressive regimens to treat and prevent GVHD and transplant rejection through the promotion of T cell tolerance." @default.
• W2533981475 created "2016-10-28" @default.
• W2533981475 creator A5050541881 @default.
• W2533981475 creator A5076800424 @default.
• W2533981475 creator A5079988714 @default.
• W2533981475 creator A5088178087 @default.
• W2533981475 date "2008-11-16" @default.
• W2533981475 modified "2023-10-03" @default.
• W2533981475 title "Enhanced Interaction Between Hsp90 and Raptor Regulates mTOR Signaling upon T Cell Activation" @default.
• W2533981475 doi "https://doi.org/10.1182/blood.v112.11.674.674" @default.
• W2533981475 hasPublicationYear "2008" @default.
• W2533981475 type Work @default.
• W2533981475 sameAs 2533981475 @default.
• W2533981475 citedByCount "1" @default.
• W2533981475 crossrefType "journal-article" @default.
• W2533981475 hasAuthorship W2533981475A5050541881 @default.
• W2533981475 hasAuthorship W2533981475A5076800424 @default.
• W2533981475 hasAuthorship W2533981475A5079988714 @default.
• W2533981475 hasAuthorship W2533981475A5088178087 @default.
• W2533981475 hasConcept C148125776 @default.
• W2533981475 hasConcept C179464577 @default.
• W2533981475 hasConcept C203014093 @default.
• W2533981475 hasConcept C2776090121 @default.
• W2533981475 hasConcept C2777949483 @default.
• W2533981475 hasConcept C62478195 @default.
• W2533981475 hasConcept C86554907 @default.
• W2533981475 hasConcept C86803240 @default.
• W2533981475 hasConcept C8891405 @default.
• W2533981475 hasConcept C95444343 @default.
• W2533981475 hasConceptScore W2533981475C148125776 @default.
• W2533981475 hasConceptScore W2533981475C179464577 @default.
• W2533981475 hasConceptScore W2533981475C203014093 @default.
• W2533981475 hasConceptScore W2533981475C2776090121 @default.
• W2533981475 hasConceptScore W2533981475C2777949483 @default.
• W2533981475 hasConceptScore W2533981475C62478195 @default.
• W2533981475 hasConceptScore W2533981475C86554907 @default.
• W2533981475 hasConceptScore W2533981475C86803240 @default.
• W2533981475 hasConceptScore W2533981475C8891405 @default.
• W2533981475 hasConceptScore W2533981475C95444343 @default.
• W2533981475 hasLocation W25339814751 @default.
• W2533981475 hasOpenAccess W2533981475 @default.
• W2533981475 hasPrimaryLocation W25339814751 @default.
• W2533981475 hasRelatedWork W1530926870 @default.
• W2533981475 hasRelatedWork W1550192924 @default.
• W2533981475 hasRelatedWork W1915431516 @default.
• W2533981475 hasRelatedWork W1968130460 @default.
• W2533981475 hasRelatedWork W1988917769 @default.
• W2533981475 hasRelatedWork W1998574940 @default.
• W2533981475 hasRelatedWork W2016867284 @default.
• W2533981475 hasRelatedWork W2025503860 @default.
• W2533981475 hasRelatedWork W2037175271 @default.
• W2533981475 hasRelatedWork W2118442804 @default.
• W2533981475 hasRelatedWork W2124069320 @default.
• W2533981475 hasRelatedWork W2135135219 @default.
• W2533981475 hasRelatedWork W2135376697 @default.
• W2533981475 hasRelatedWork W2138287291 @default.
• W2533981475 hasRelatedWork W2156239323 @default.
• W2533981475 hasRelatedWork W2162432337 @default.
• W2533981475 hasRelatedWork W2277337138 @default.
• W2533981475 hasRelatedWork W2325555899 @default.
• W2533981475 hasRelatedWork W2563230450 @default.
• W2533981475 hasRelatedWork W2566919111 @default.
• W2533981475 isParatext "false" @default.
• W2533981475 isRetracted "false" @default.
• W2533981475 magId "2533981475" @default.
• W2533981475 workType "article" @default.