Activation via the antigen receptors triggers a
cascade of intracellular biochemical events eventually
leading to lymphocyte proliferation and effector functions.
For the past few years, our research is focused on
understanding how membrane-associated adaptor molecules
function in lymphocyte development and activation.
We have been working on three different adaptor molecules:
LAT, LAX, and LAB. LAT is an adaptor molecule that
is essential for T cell activation and thymocyte development.
By using a series of LAT Tyr to Phe mutants, we have
identified the critical tyrosine residues of LAT function.
In addition, we further examined the importance of
LAT localization to lipid rafts in LAT function. LAX
is an adaptor molecule that we identified recently.
It is predominantly expressed in T, B, and mast cells.
It shares similar tyrosine motifs as those in LAT.
Upon stimulation via the B or T cell receptors, LAX
is rapidly phosphorylated by Src and Syk family tyrosine
kinases and interacts with Grb2, Gads, and the p85
subunit of PI-3 kinase. Overexpression of LAX in T
cells inhibits T cell receptor-mediated p38 MAPK activation
and NFAT/AP-1 transcriptional activation. Our data
suggested that LAX functions to negatively regulate
signaling in lymphocytes. In addition to LAT and LAX,
we also discovered another adaptor, named LAB. This
molecule is expressed in B cells, mast cells, and
NK cells. It is localized to lipid rafts like LAT.
It can bind Grb2 and Gads, however, not PLC-g1 or
PLC-g2. Our data suggested that it might function
similarly to LAT.
