Zhang W, Trible R P, Samelson L E
Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.
Immunity. 1998 Aug;9(2):239-46. doi: 10.1016/s1074-7613(00)80606-8.
The linker molecule LAT is a critical substrate of the tyrosine kinases activated upon TCR engagement. Phosphorylated LAT binds Grb2, PLC-gamma1, and other signaling molecules. We demonstrate that human LAT is palmitoylated and that palmitoylated LAT predominantly localizes into glycolipid-enriched microdomains (GEMs). Although the LAT transmembrane domain is sufficient for membrane localization, palmitoylation at C26 and C29 is essential for efficient partitioning into GEMs. LAT palmitoylation is necessary for its tyrosine phosphorylation. After T cell activation, most tyrosine-phosphorylated LAT molecules and a fraction of PLC-gamma1 and other signaling molecules are present in GEMs. LAT is central to T cell activation and is a novel linker molecule shown to require targeting to membrane microdomains for signaling.
接头分子LAT是TCR参与后被激活的酪氨酸激酶的关键底物。磷酸化的LAT与Grb2、PLC-γ1及其他信号分子结合。我们证明人LAT被棕榈酰化，且棕榈酰化的LAT主要定位于富含糖脂的微结构域（GEMs）。尽管LAT跨膜结构域足以实现膜定位，但C26和C29位的棕榈酰化对于有效分配至GEMs至关重要。LAT的棕榈酰化对于其酪氨酸磷酸化是必需的。T细胞活化后，大多数酪氨酸磷酸化的LAT分子以及一部分PLC-γ1和其他信号分子存在于GEMs中。LAT是T细胞活化的核心，是一种新型接头分子，已证明其信号传导需要靶向膜微结构域。
