MGSSHHHHHH SSGLVPRGSH MRCSRPGAKR SEKIYQQRSL REDQQSFTGS RTYSLVGQAW PGPLADMAPT RKDKLLQFYP SLEDPASSRY QNFSKGSRHG SEEAYIDPIA MEYYNWGRFS KPPEDDDANS YENVLICKQK TTETGAQQEG IGGLCRGDLS LSLALKTGPT SGLCPSASPE EDEESEDYQN SASIHQWRES RKVMGQLQRE ASPGPVGSPD EEDGEPDYVN GEVAATEA.
Non-T-cell Activation Linker (NTAL), also known as Linker for Activation of B cells (LAB), is a transmembrane adaptor protein. It is structurally and evolutionarily related to the Linker for Activation of T cells (LAT). NTAL is expressed in various immune cells, including B cells, natural killer (NK) cells, mast cells, and macrophages .
NTAL is a 30 kDa double-palmitoylated protein. It is rapidly phosphorylated after the engagement of B cell receptors (BCR) or Fc receptors (FcR) . The protein is encoded by the WBSCR5 gene, which is located in the Williams-Beuren syndrome chromosomal region . The amino acid sequence of NTAL includes several tyrosine residues that become phosphorylated upon activation, facilitating the recruitment of downstream signaling molecules .
NTAL plays a crucial role in the negative regulation of early stages of BCR-dependent B cell signaling. It serves as a negative regulator in mast cells as well, although it also contributes to some activation processes in these cells, partially overlapping with LAT function . In T cells, NTAL negatively regulates T cell receptor (TCR) signaling, which is essential to avoid uncontrolled immune responses .
Recent studies have shown that NTAL expression in Jurkat cells, a model for T cells, decreases calcium fluxes and PLC-γ1 activation upon stimulation through the TCR complex . This suggests that NTAL has a potential role in autoimmune disorders, such as rheumatoid arthritis, by negatively regulating TCR signaling .
Recombinant NTAL proteins are used in various research applications, including blocking assays and control experiments . These proteins are typically expressed in systems like E. coli and purified for use in laboratory settings .