PMID- 10072481
OWN - NLM
STAT- MEDLINE
DCOM- 19990414
LR  - 20071115
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 162
IP  - 5
DP  - 1999 Mar 1
TI  - Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated
      cytotoxicity.
PG  - 2453-6
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
      FcgammaRIII 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-gamma. 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.
FAU - Jevremovic, D
AU  - Jevremovic D
AD  - Department of Immunology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
FAU - Billadeau, D D
AU  - Billadeau DD
FAU - Schoon, R A
AU  - Schoon RA
FAU - Dick, C J
AU  - Dick CJ
FAU - Irvin, B J
AU  - Irvin BJ
FAU - Zhang, W
AU  - Zhang W
FAU - Samelson, L E
AU  - Samelson LE
FAU - Abraham, R T
AU  - Abraham RT
FAU - Leibson, P J
AU  - Leibson PJ
LA  - eng
GR  - CA-09441/CA/NCI NIH HHS/United States
GR  - CA-47752/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (LAT protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoproteins)
RN  - EC 3.1.4.- (Type C Phospholipases)
SB  - AIM
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Carrier Proteins/physiology
MH  - Cell Line
MH  - *Cytotoxicity, Immunologic
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Lymphocyte Activation
MH  - *Membrane Proteins
MH  - Phosphoproteins/physiology
MH  - Type C Phospholipases/physiology
EDAT- 1999/03/11 00:00
MHDA- 1999/03/11 00:01
CRDT- 1999/03/11 00:00
PHST- 1999/03/11 00:00 [pubmed]
PHST- 1999/03/11 00:01 [medline]
PHST- 1999/03/11 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1999 Mar 1;162(5):2453-6.