Matches in SemOpenAlex for { <https://semopenalex.org/work/W2034197022> ?p ?o ?g. }
Showing items 1 to 73 of
73
with 100 items per page.
- W2034197022 endingPage "S229" @default.
- W2034197022 startingPage "S229" @default.
- W2034197022 abstract "889 Ligands of the T cell receptor (TCR) with agonist or partial agonist/antagonist properties can be generated by conservative mutations in the TCR contact points of the immunogenic peptide or the MHC molecule. The biological effects following TCR engagement with partial agonist/antagonist ligands range from split effector T cell function (e.g., cytokine production without proliferation) to induction of T cell anergy. Based on the antigen-specific nature of these effects, TCR partial agonists/antagonists may be very valuable immunosuppressive agents in transplantation. We have previously shown that TCR partial agonists induce a distinct signalling pattern characterized by incomplete phosphorylation of TCR subunits without activation of lck and ZAP-70 kinase activities. However these variant ligands of the TCR are able to activate the Ras-Mitogen Activated Protein Kinase (MAPK) pathway to a similar extent as agonists do, albeit in a more transient manner. This finding lead us to propose that there is a ZAP-70-independent pathway of Ras-MAPK activation. The characterization of the molecular basis of this pathway is valuable to identify biochemical steps in the induction of specific T cell effector functions. Here, we demonstrate that the activation of the Ras-MAPK pathway by partial agonists of the TCR does not involve tyrosine phosphorylation of the linker for T cell activation (LAT) protein. Rather, they induce primary recruitment of Grb2-SOS complexes to the TCR. The association of Grb2 to TCR ζ may be indirect through SHC, since we have observed that partial agonists induce significant tyrosine phosphorylation of this molecule. The recruitment of Grb2-SOS complexes to engaged TCR would then determine the proximity of SOS with Ras and subsequent activation of the MAPK pathway. Our data provides an explanation for differential activation of the Ras-MAPK pathway by TCR partial agonists, without concomitant activation of lck or ZAP-70 and subsequent phosphorylation of LAT. Modulation of the TCR-Grb2-SOS association may prove a suitable target for the development of immunomodulatory drugs." @default.
- W2034197022 created "2016-06-24" @default.
- W2034197022 creator A5011133492 @default.
- W2034197022 creator A5056785682 @default.
- W2034197022 date "1999-04-01" @default.
- W2034197022 modified "2023-09-26" @default.
- W2034197022 title "PARTIAL AGONISTS OF THE T CELL RECEPTOR ACTIVATE THE Ras-MAPK PATHWAY IN A LAT-INDEPENDENT MANNER" @default.
- W2034197022 doi "https://doi.org/10.1097/00007890-199904150-00913" @default.
- W2034197022 hasPublicationYear "1999" @default.
- W2034197022 type Work @default.
- W2034197022 sameAs 2034197022 @default.
- W2034197022 citedByCount "0" @default.
- W2034197022 crossrefType "journal-article" @default.
- W2034197022 hasAuthorship W2034197022A5011133492 @default.
- W2034197022 hasAuthorship W2034197022A5056785682 @default.
- W2034197022 hasBestOaLocation W20341970221 @default.
- W2034197022 hasConcept C11960822 @default.
- W2034197022 hasConcept C148125776 @default.
- W2034197022 hasConcept C170493617 @default.
- W2034197022 hasConcept C177917778 @default.
- W2034197022 hasConcept C185592680 @default.
- W2034197022 hasConcept C19317047 @default.
- W2034197022 hasConcept C203014093 @default.
- W2034197022 hasConcept C2776090121 @default.
- W2034197022 hasConcept C2777553839 @default.
- W2034197022 hasConcept C2778938600 @default.
- W2034197022 hasConcept C42362537 @default.
- W2034197022 hasConcept C55493867 @default.
- W2034197022 hasConcept C57074206 @default.
- W2034197022 hasConcept C58732023 @default.
- W2034197022 hasConcept C62478195 @default.
- W2034197022 hasConcept C86803240 @default.
- W2034197022 hasConcept C8891405 @default.
- W2034197022 hasConcept C95444343 @default.
- W2034197022 hasConceptScore W2034197022C11960822 @default.
- W2034197022 hasConceptScore W2034197022C148125776 @default.
- W2034197022 hasConceptScore W2034197022C170493617 @default.
- W2034197022 hasConceptScore W2034197022C177917778 @default.
- W2034197022 hasConceptScore W2034197022C185592680 @default.
- W2034197022 hasConceptScore W2034197022C19317047 @default.
- W2034197022 hasConceptScore W2034197022C203014093 @default.
- W2034197022 hasConceptScore W2034197022C2776090121 @default.
- W2034197022 hasConceptScore W2034197022C2777553839 @default.
- W2034197022 hasConceptScore W2034197022C2778938600 @default.
- W2034197022 hasConceptScore W2034197022C42362537 @default.
- W2034197022 hasConceptScore W2034197022C55493867 @default.
- W2034197022 hasConceptScore W2034197022C57074206 @default.
- W2034197022 hasConceptScore W2034197022C58732023 @default.
- W2034197022 hasConceptScore W2034197022C62478195 @default.
- W2034197022 hasConceptScore W2034197022C86803240 @default.
- W2034197022 hasConceptScore W2034197022C8891405 @default.
- W2034197022 hasConceptScore W2034197022C95444343 @default.
- W2034197022 hasIssue "7" @default.
- W2034197022 hasLocation W20341970221 @default.
- W2034197022 hasOpenAccess W2034197022 @default.
- W2034197022 hasPrimaryLocation W20341970221 @default.
- W2034197022 hasRelatedWork W102043283 @default.
- W2034197022 hasRelatedWork W1577207606 @default.
- W2034197022 hasRelatedWork W1693076983 @default.
- W2034197022 hasRelatedWork W1986771544 @default.
- W2034197022 hasRelatedWork W1995507496 @default.
- W2034197022 hasRelatedWork W2090555440 @default.
- W2034197022 hasRelatedWork W2096118127 @default.
- W2034197022 hasRelatedWork W2120071583 @default.
- W2034197022 hasRelatedWork W4313333707 @default.
- W2034197022 hasRelatedWork W4313383272 @default.
- W2034197022 hasVolume "67" @default.
- W2034197022 isParatext "false" @default.
- W2034197022 isRetracted "false" @default.
- W2034197022 magId "2034197022" @default.
- W2034197022 workType "article" @default.