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Signal transduction by the T-cell antigen receptor: Regulation and function of p21ras and PtdIns-3 kinase

AutorCantrell, Doreen A.; Izquierdo, Manuel ; Reif, K.; Woodrow, M.
Fecha de publicación1994
EditorS. Karger AG
CitaciónChemical Immunology 59: 115-127 (1994)
ResumenThe term 'T-cell activation' commonly refers to the events triggered by antigen stimulation that culminate in the production of cytokines such as interleukin-2 (IL-2) and the expression of cytokine receptors such as the IL-2 receptor. The physiologival trigger for T-cell activation is engagement of the T-cell antigen receptor (TCR) with antigen/major histocompatibility molecules presented to the T cell on the surface of an atigen presenting cell,. the TCR is a multichain complex comprising a sisulfide-linked heterodimer of the idiotypic αβ-chain noncovalently associated witha signal transduction complex composed of the invariant CD3 γ-, δ-, ε-chains and the ξ- (16 kD) and η- (22 kD) subunits. Triggering of the TCR/CD3 complex initiates a cascade of biochemical events, the earlies of which is activation of intracellular protein tyrosine kinases (PTKs). This activation of PTKs appears to be absolutely required for all subsequent T cell responses. The cytoplasmic domains of the CD3 and ξ-subunits contain a common motif D/EX7D/EX2YX2L/IX7YX2L/I which is present in a single copy in each of the CD3 chains and triplicated in the ξ-subunit. This evolutionarily conserved activation motif is crucial for TCR coupling to intracellular PTKs. PTKs involved in TCR signal transduction are the src family kinases p56lck and p59fyn and a 70-kD PTK termed ZAP70. The relative contribution of p56lck, p59fyn, and ZAP70 to TCR/CD3 signal transduction has been reviewed extensively elsewhere. The object of the present review is to discuss the distal signalling pathways coupled to the TCR by PTKs.
Identificadoresissn: 1015-0145
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