Regulation of lymphocyte development and activation by the LAT family of adapter proteins

Abstract

The LAT Family of Adaptor Proteins Transmembrane adaptor proteins (TRAPs) are critical components of signaling pathways in lymphocytes, linking antigen receptor engagement to downstream cellular processes. While these proteins lack intrinsic enzymatic activity, their phosphorylation following receptor ligation allows them to function as scaffolds for the assembly of multi-molecular signaling complexes. Many TRAPs have recently been discovered and numerous studies demonstrate their roles in the positive and negative regulation of lymphocyte maturation, activation, and differentiation. One such example is the LAT (linker for activation of T cells) family of adaptor proteins. While LAT has been shown to play an indispensable role in T cell and mast cell function, the other family members, LAB (linker for activation of B cells) and LAX (linker for activation of X cells), are necessary to fine-tune immune responses. In addition to its well-established role in the positive regulation of lymphocyte activation, LAT exerts an inhibitory effect on TCR (T cell receptor)-mediated signaling. Furthermore, LAT, along with LAB and LAX, plays a crucial role in establishing and maintaining tolerance. Here, we review recent data concerning the regulation of lymphocyte development and activation by the LAT family of proteins.

Control of Transplant Tolerance and Intragraft Regulatory T Cell Localization by Myeloid-Derived Suppressor Cells and CCL5

“…Microarray analyses revealed two interesting features that could shed light on our previous results. First, the expression of LAT, a gene coding for a transmembrane adaptor protein (38), was significantly downregulated in MDSC from tolerant recipients. LAT is known to be expressed in thymocytes, mature T cells, NK cells, mast cells, megakaryoctes, and pre-B cells (39)(40)(41) and is an essential regulator of cell activation, terminal differentiation (42), and maturation (43).…”

SCIMP, a Transmembrane Adaptor Protein Involved in Major Histocompatibility Complex Class II Signaling

“…LAT interacts with the SLP family adaptor SLP76 and transduces signals of similar types to those transduced by SCIMP (16). However, the range of receptors employing SCIMP as a signal transducer will most likely be different due to its association with TEMs.…”

“…TCR engagement in the IS leads to subsequent activation of Src and Syk family kinases and tyrosine phosphorylation of a number of molecules, including the transmembrane adaptor protein (TRAP) LAT. LAT is a critical component of several signaling pathways, mainly due to its ability to recruit a complex of phospholipase C gamma 1 (PLC-␥1) with the adaptors Gads and SLP76 (16).…”

Tyrosine Phosphorylation-Independent Regulation of Lipopolysaccharide-Mediated Response by the Transmembrane Adaptor Protein LAB

“…Upon the engagement of immunoreceptors, transmembrane adaptor proteins (TRAPs) are phosphorylated on multiple tyrosine residues and serve as scaffolds that recruit SH2-containing proteins to the plasma membrane and ultimately cause the activation of downstream signaling cascades(1–3). One of the most studied TRAPs is LAT (linker for activation of T cells).…”