title: The transmembrane adapter LAT plays a central role in immune receptor signalling.
abstract: The transmembrane adapter LAT (linker for activation of T cells) plays a central role in signalling by ITAM bearing receptors expressed on T cells, natural killer cells, mast cells and platelets. Receptor engagement leads to the phosphorylation of tyrosine residues present in the intracellular domain of LAT and formation of a multiprotein complex with other adapter molecules and enzymes including Grb2, Gads/SLP-76 and PLCgamma isoforms. These signalling events predominantly take place in glycolipid-enriched membrane domains. 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 emphasizes 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.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. peter.wonerow@phsrm.ox.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Wonerow
authors.forename: S P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D008565:Membrane Proteins; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D014443:Tyrosine; D010738:Type C Phospholipases