TY - JOUR
T1 - Cutting edge
T2 - A role for the adaptor protein LAT in human NK cell- mediated cytotoxicity
AU - Jevremovic, Dragan
AU - Billadeau, Daniel D.
AU - Schoon, Renee A.
AU - Dick, Christopher J.
AU - Irvin, Brenda J.
AU - Zhang, Weiguo
AU - Samelson, Lawrence E.
AU - Abraham, Robert T.
AU - Leibson, Paul J.
PY - 1999/3/1
Y1 - 1999/3/1
N2 - Stimulation of NK cell-mediated cytotoxicity involves the coupling of proximal Src and Syk family protein tyrosine kinases to downstream effectors. However, the mechanisms linking these second messenger pathways are incompletely understood. Here, we describe a key role for the LAT (p36) adaptor protein in human NK cell activation. LAT is tyrosine phosphorylated upon stimulation of NK cells through FcγRIII receptors and following direct contact with NK-sensitive target cells. This NK stimulation induces the association of LAT with several phosphotyrosine-containing proteins. In addition to the biochemical evidence showing LAT involvement in NK cell activation, a genetic model shows that LAT is required for FcR-dependent phosphorylation of phospholipase C-γ. Furthermore, overexpression of LAT in NK cells leads to increased Ab-dependent cell-mediated cytotoxicity and 'natural cytotoxicity,' thus demonstrating a functional role for LAT in NK cells. These data suggest that LAT is an important adaptor protein for the regulation of human NK cell-mediated cytotoxicity.
AB - Stimulation of NK cell-mediated cytotoxicity involves the coupling of proximal Src and Syk family protein tyrosine kinases to downstream effectors. However, the mechanisms linking these second messenger pathways are incompletely understood. Here, we describe a key role for the LAT (p36) adaptor protein in human NK cell activation. LAT is tyrosine phosphorylated upon stimulation of NK cells through FcγRIII receptors and following direct contact with NK-sensitive target cells. This NK stimulation induces the association of LAT with several phosphotyrosine-containing proteins. In addition to the biochemical evidence showing LAT involvement in NK cell activation, a genetic model shows that LAT is required for FcR-dependent phosphorylation of phospholipase C-γ. Furthermore, overexpression of LAT in NK cells leads to increased Ab-dependent cell-mediated cytotoxicity and 'natural cytotoxicity,' thus demonstrating a functional role for LAT in NK cells. These data suggest that LAT is an important adaptor protein for the regulation of human NK cell-mediated cytotoxicity.
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M3 - Article
C2 - 10072481
AN - SCOPUS:0033104767
SN - 0022-1767
VL - 162
SP - 2453
EP - 2456
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -