The role of membrane rafts in Lck transport, regulation and signalling in T-cells.

ABSTRACT

Tyrosine phosphorylation is one of the key covalent modifications that occur in multicellular organisms. Since its discovery more than 30 years ago, tyrosine phosphorylation has come to be understood as a fundamentally important mechanism of signal transduction and regulation in all eukaryotic cells. The tyrosine kinase Lck (lymphocyte-specific protein tyrosine kinase) plays a crucial role in the T-cell response by transducing early activation signals triggered by TCR (T-cell receptor) engagement. These signals result in the phosphorylation of immunoreceptor tyrosine-based activation motifs present within the cytosolic tails of the TCR-associated CD3 subunits that, once phosphorylated, serve as scaffolds for the assembly of a large supramolecular signalling complex responsible for T-cell activation. The existence of membrane nano- or micro-domains or rafts as specialized platforms for protein transport and cell signalling has been proposed. The present review discusses the signals that target Lck to membrane rafts and the importance of these specialized membranes in the transport of Lck to the plasma membrane, the regulation of Lck activity and the phosphorylation of the TCR.