The transmembrane adapter LAT (linker for activation of T cells) plays a ce
ntral role in signalling by ITAM bearing receptors expressed on T cells, na
tural killer cells, mast cells and platelets. Receptor engagement leads to
the phosphorylation of tyrosine residues present in the intracellular domai
n of LAT and formation of a multiprotein complex with other adapter molecul
es and enzymes including Grb2, Gads/SLP-76 and PLC gamma isoforms. These si
gnalling events predominantly take place in glycolipid-enriched membrane do
mains. The constitutive presence of LAT in GEMs enables its function as the
main scaffolding protein for the organization of GEM-localized signalling.
The study of LAT-deficient mice and LAT-deficient cell lines further empha
sizes the importance of LAT for these signalling cascades but also defines
the existence of LAT-independent events downstream of the Syk-family kinase
-ITAM complex.