LAT (Concentrate)

Full Name

linker for activation of T cells

Function

Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development. Involved in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules.

Biological Process

Adaptive immune responseIEA:UniProtKB-KW
Calcium-mediated signalingManual Assertion Based On ExperimentIMP:HGNC-UCL
Gene expressionIEA:Ensembl
Immune responseManual Assertion Based On ExperimentIDA:HGNC-UCL
Inflammatory responseManual Assertion Based On ExperimentIBA:GO_Central
Integrin-mediated signaling pathwayManual Assertion Based On ExperimentIDA:HGNC-UCL
Intracellular signal transductionManual Assertion Based On ExperimentIDA:HGNC-UCL
Lymphocyte homeostasisIEA:Ensembl
Mast cell degranulationIEA:UniProtKB-KW
Positive regulation of protein kinase activityManual Assertion Based On ExperimentIEP:CACAO
Ras protein signal transductionManual Assertion Based On ExperimentIMP:HGNC-UCL
Regulation of T cell activationManual Assertion Based On ExperimentIMP:HGNC-UCL
T cell activationManual Assertion Based On ExperimentTAS:UniProtKB

Cellular Location

Cell membrane
Present in lipid rafts.

Involvement in disease

Immunodeficiency 52 (IMD52):
An autosomal recessive primary immunodeficiency characterized by T-cell abnormalities, resulting in severe combined immunodeficiency, autoimmune disease, progressive lymphopenia and hypogammaglobulinemia, and lymphoproliferation with splenomegaly. Patients develop severe recurrent infections from infancy.

Topology

Extracellular: 1-4
Helical: 5-27
Cytoplasmic: 28-262

PTM

Phosphorylated on tyrosines by ZAP70 upon TCR activation, or by SYK upon other immunoreceptor activation; which leads to the recruitment of multiple signaling molecules. Is one of the most prominently tyrosine-phosphorylated proteins detected following TCR engagement. May be dephosphorylated by PTPRJ. Phosphorylated by ITK leading to the recruitment of VAV1 to LAT-containing complexes.
Palmitoylation of Cys-26 and Cys-29 is required for raft targeting and efficient phosphorylation.