Linker for activation of T cells (LAT)

Linker for activation of T cells (LAT) is a single-pass transmembrane adaptor protein of approximately 36–38 kDa, essential for T cell receptor (TCR) signaling and T cell development[1][2][3][4][5]. Expressed predominantly in T cells, natural killer (NK) cells, mast cells, and platelets, LAT acts as a critical scaffold at the plasma membrane, where it localizes to lipid rafts via palmitoylation at juxtamembrane cysteine residues (C26, C29)[3][4]. After TCR engagement and activation of the tyrosine kinase ZAP-70, LAT is phosphorylated at multiple conserved tyrosine residues, creating binding sites for SH2 domain–containing signaling proteins (such as PLCγ1, Grb2, Gads, and SLP-76)[1][3][4]. Phosphorylated LAT assembles multiprotein complexes that initiate downstream signaling cascades, ultimately activating transcription factors including NF-κB, NFAT, and AP-1, which regulate genes important for immune response, proliferation, survival, and cytokine production[2][3][4][5]. Deficiency or mutation of LAT severely impairs T cell development and function, and may lead to immune dysregulation or disease[2][5]. LAT also serves as an integration node for costimulatory and adhesion receptors (such as CD2, CD5, CD9, and CD28), ensuring precise spatiotemporal signal processing necessary for proper adaptive immune responses[2][3]. No approved drugs currently target LAT directly, and there are no established clinical pharmacodynamic biomarkers or mechanisms of action described for targeting this adaptor protein in therapeutic settings. Given its central role in immune cell signaling, therapeutic manipulation of LAT carries risks, such as immunodeficiency or pathological immune activation, highlighting important safety concerns[2][3][5].

Other names

Linker of activated T cellsLinker for activation of T-cells family member 1LAT1pp3636 kDa phosphotyrosine adapter proteinp36-3836 kDa phospho-tyrosine adapter/adaptor proteinIMD52