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Andrew C Chan - One of the best experts on this subject based on the ideXlab platform.

  • T Cell recepTor signaling precedes immunological synapse formaTion
    Science, 2002
    Co-Authors: Kyeonghee Lee, Michael L Dustin, Amy D Holdorf, Andrew C Chan, Paul M Allen, Andrey S Shaw
    Abstract:

    The area of conTacT beTween a T Cell and an anTigen-presenTing Cell (APC) is known as The immunological synapse. AlThough iTs exacT funcTion is unknown, one model suggesTs ThaT iT allows for T Cell recepTor (TCR) clusTering and for susTained signaling in T Cells for many hours. Here we demonsTraTe ThaT TCR-mediaTed Tyrosine kinase signaling in naive T Cells occurred primarily aT The periphery of The synapse and was largely abaTed before maTure immunological synapses had formed. These daTa suggesT ThaT many hours of TCR signaling are noT required for T Cell acTivaTion. These observaTions challenge currenT ideas abouT The role of immunological synapses in T Cell acTivaTion.

  • phosphorylaTion of slp 76 by The zap 70 proTein Tyrosine kinase is required for T Cell recepTor funcTion
    Journal of Biological Chemistry, 1996
    Co-Authors: Juliane Bubeck Wardenburg, Andrew C Chan, Janet K Jackman, Horst Flotow, Sandra E Wilkinson, David Williams, Robin Johnson, Guanghui Kong, Paul R Findell
    Abstract:

    AbsTracT Two families of Tyrosine kinases, The Src and Syk families, are required for T-Cell recepTor acTivaTion. While The Src kinases are responsible for phosphorylaTion of recepTor-encoded signaling moTifs and for up-regulaTion of ZAP-70 acTiviTy, The downsTream subsTraTes of ZAP-70 are unknown. Evidence is presenTed herein ThaT The Src homology 2 (SH2) domain-conTaining leukocyTe proTein of 76 kDa (SLP-76) is a subsTraTe of ZAP-70. PhosphorylaTion of SLP-76 is diminished in T Cells ThaT express a caTalyTically inacTive ZAP-70. Moreover, SLP-76 is preferenTially phosphorylaTed by ZAP-70 in viTro and in heTerologous Cellular sysTems. In T Cells, overexpression of wild-Type SLP-76 resulTs in a hyperacTive recepTor, while expression of a SLP-76 molecule ThaT is unable To be Tyrosine-phosphorylaTed aTTenuaTes recepTor funcTion. In addiTion, The SH2 domain of SLP-76 is required for T-Cell recepTor funcTion, alThough iTs role is independenT of The abiliTy of SLP-76 To undergo Tyrosine phosphorylaTion. As SLP-76 inTeracTs wiTh boTh Grb2 and phospholipase C-γ1, These daTa indicaTe ThaT phosphorylaTion of SLP-76 by ZAP-70 provides an imporTanT funcTional link beTween The T-Cell recepTor and acTivaTion of ras and calcium paThways.

Hans Jörg Fehling - One of the best experts on this subject based on the ideXlab platform.

  • crucial role of The pre T Cell recepTor α gene in developmenT of ap buT noT γδ T Cells
    Nature, 1995
    Co-Authors: Hans Jörg Fehling, Anna Krotkova, Claude Saintruf, Harald Von Boehmer
    Abstract:

    IN T-Cell precursors, The T-Cell-recepTor β chain is expressed before The T-Cell-recepTor α chain1,2 and is sufficienT To advance T-Cell developmenT in The absence of T-Cell recepTor α chains3–7. In immaTure T Cells, The T-Cell-recepTor β proTein can form disulphide-linked heTerodimers wiTh The pre-T-Cell-recepTor α chain8,9 and associaTe wiTh signal-Transducing CD3 molecules5. The recenTly cloned pre-T-Cell-recepTor a gene encodes a Transmembrane proTein ThaT is expressed in immaTure buT noT maTure T Cells9,10. Here we show ThaT αβ, buT noT γδ, Cell developmenT is severely hampered in pre-T-Cell-recepTor α-gene-deficienT mice, which esTablishes a crucial role for The pre-T-Cell recepTor in early ThymocyTe developmenT.

  • crucial role of The pre T Cell recepTor alpha gene in developmenT of alpha beTa buT noT gamma delTa T Cells
    Nature, 1995
    Co-Authors: Hans Jörg Fehling, Anna Krotkova, Claude Saintruf, H Von Boehmer
    Abstract:

    In T-Cell precursors, The T-Cell-recepTor beTa chain is expressed before The T-Cell-recepTor alpha chain and is sufficienT To advance T-Cell developmenT in The absence of T-Cell recepTor alpha chains. In immaTure T Cells, The T-Cell-recepTor beTa proTein can form disulphide-linked heTerodimers wiTh The pre-T-Cell-recepTor alpha chain and associaTe wiTh signal-Transducing CD3 molecules. The recenTly cloned pre-T-Cell-recepTor alpha gene encodes a Transmembrane proTein ThaT is expressed in immaTure buT noT maTure T Cells. Here we show ThaT alpha beTa, buT noT gamma delTa, Cell developmenT is severely hampered in pre-T-Cell-recepTor alpha-gene-deficienT mice, which esTablishes a crucial role for The pre-T-Cell recepTor in early ThymocyTe developmenT.

Paul R Findell - One of the best experts on this subject based on the ideXlab platform.

  • phosphorylaTion of slp 76 by The zap 70 proTein Tyrosine kinase is required for T Cell recepTor funcTion
    Journal of Biological Chemistry, 1996
    Co-Authors: Juliane Bubeck Wardenburg, Andrew C Chan, Janet K Jackman, Horst Flotow, Sandra E Wilkinson, David Williams, Robin Johnson, Guanghui Kong, Paul R Findell
    Abstract:

    AbsTracT Two families of Tyrosine kinases, The Src and Syk families, are required for T-Cell recepTor acTivaTion. While The Src kinases are responsible for phosphorylaTion of recepTor-encoded signaling moTifs and for up-regulaTion of ZAP-70 acTiviTy, The downsTream subsTraTes of ZAP-70 are unknown. Evidence is presenTed herein ThaT The Src homology 2 (SH2) domain-conTaining leukocyTe proTein of 76 kDa (SLP-76) is a subsTraTe of ZAP-70. PhosphorylaTion of SLP-76 is diminished in T Cells ThaT express a caTalyTically inacTive ZAP-70. Moreover, SLP-76 is preferenTially phosphorylaTed by ZAP-70 in viTro and in heTerologous Cellular sysTems. In T Cells, overexpression of wild-Type SLP-76 resulTs in a hyperacTive recepTor, while expression of a SLP-76 molecule ThaT is unable To be Tyrosine-phosphorylaTed aTTenuaTes recepTor funcTion. In addiTion, The SH2 domain of SLP-76 is required for T-Cell recepTor funcTion, alThough iTs role is independenT of The abiliTy of SLP-76 To undergo Tyrosine phosphorylaTion. As SLP-76 inTeracTs wiTh boTh Grb2 and phospholipase C-γ1, These daTa indicaTe ThaT phosphorylaTion of SLP-76 by ZAP-70 provides an imporTanT funcTional link beTween The T-Cell recepTor and acTivaTion of ras and calcium paThways.

H Von Boehmer - One of the best experts on this subject based on the ideXlab platform.

  • crucial role of The pre T Cell recepTor alpha gene in developmenT of alpha beTa buT noT gamma delTa T Cells
    Nature, 1995
    Co-Authors: Hans Jörg Fehling, Anna Krotkova, Claude Saintruf, H Von Boehmer
    Abstract:

    In T-Cell precursors, The T-Cell-recepTor beTa chain is expressed before The T-Cell-recepTor alpha chain and is sufficienT To advance T-Cell developmenT in The absence of T-Cell recepTor alpha chains. In immaTure T Cells, The T-Cell-recepTor beTa proTein can form disulphide-linked heTerodimers wiTh The pre-T-Cell-recepTor alpha chain and associaTe wiTh signal-Transducing CD3 molecules. The recenTly cloned pre-T-Cell-recepTor alpha gene encodes a Transmembrane proTein ThaT is expressed in immaTure buT noT maTure T Cells. Here we show ThaT alpha beTa, buT noT gamma delTa, Cell developmenT is severely hampered in pre-T-Cell-recepTor alpha-gene-deficienT mice, which esTablishes a crucial role for The pre-T-Cell recepTor in early ThymocyTe developmenT.

David Baltimore - One of the best experts on this subject based on the ideXlab platform.

  • funcTion of The pre T Cell recepTor alpha chain in T Cell developmenT and allelic exclusion aT The T Cell recepTor beTa locus
    Proceedings of the National Academy of Sciences of the United States of America, 1996
    Co-Authors: Laurie Davidson, Frederick W Alt, David Baltimore
    Abstract:

    The pre-T-Cell recepTor, composed of The T-Cell recepTor (TCR) beTa chain (TCRbeTa), pre-Talpha (pTalpha) chain, and CD3 molecules, has been posTulaTed To be a Transducer of signals during The early sTages of T-Cell developmenT. To examine The funcTion of The Transmembrane pTalpha chain during TbymocyTe developmenT, we generaTed pTalpha-/- embryonic sTem Cells and assayed Their abiliTy To differenTiaTe inTo lymphoid Cells in vivo afTer injecTion inTo recombinaTion-acTivaTing gene (RAG)-2-deficienT blasTocysTs. ThymocyTes represenTing all sTages of T-Cell differenTiaTion were deTecTed in The Thymus of pTalpha-/- chimeric mice, indicaTing ThaT ThymocyTe developmenT can occur wiThouT pTalpha. However, greaTly reduced ThymocyTe numbers and subsTanTially increased percenTages of boTh CD4-CD8- ThymocyTes and TCRgammadelTa+ ThymocyTes suggesT ThaT pTalpha plays a criTical role in ThymocyTe expansion. To invesTigaTe The role of The pTalpha chain in allelic exclusion aT The TCRbeTa locus, a funcTionally rearranged TCRbeTa minigene was inTroduced inTo pTalpha-/- and pTalpha+/- embryonic sTem Cells, which were subsequenTly assayed by RAG-2-deficienT blasTocysT complemenTaTion. In The absence of pTalpha, expression of The Transgenic TCRbeTa inhibiTed rearrangemenT of The endogenous TCRbeTa locus To an exTenT similar To ThaT seen in normal TCRbeTa Transgenic mice, suggesTing ThaT pTalpha may noT be required for signaling allelic exclusion aT The TCRbeTa locus.