Lck and the nature of the T cell receptor trigger
Davis SJ, van der Merwe PA. (2011), Trends Immunol. 32, 1-5
Exactly how ligand binding ‘triggers’ T cell receptor (TCR) phosphorylation is unclear. It has been proposed that ligand engagement by the TCR somehow activates the Src kinase Lck, which in turn phosphorylates the receptor. Recent data, however, suggest instead that a significant fraction of the Lck in resting T cells is already activated and that the proportion of active Lck does not change during the early stages of T cell activation. We argue that, caveats notwithstanding, these new observations offer support for the ‘kinetic-segregation’ model of TCR triggering, which involves spatial reorganization of signalling proteins upon ligand binding and requires a fraction of Lck to be active in resting T cells.
Key figure: Lck regulation by phosphorylation
The active, inactive and ‘primed’ isoforms of Lck, and their interconversion via phosphorylation by Csk and by Lck itself, and via CD45-mediated dephosphorylation, are illustrated. The SH3, SH2 and tyrosine kinase domains of Lck are represented as triangles, squares and ovals, respectively. Yellow and green stars are used to denote Tyr394 and Tyr505 phosphorylation, respectively. The relative proportions of each of the Lck isoforms in unstimulated human CD4+ T cells, measured in a recent study , are indicated in the blue circles.