Cutting edge

A role for the adaptor protein LAT in human NK cell- mediated cytotoxicity

Dragan Jevremovic, Daniel D Billadeau, Renee A. Schoon, Christopher J. Dick, Brenda J. Irvin, Weiguo Zhang, Lawrence E. Samelson, Robert T. Abraham, Paul J. Leibson

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2453-2456
Number of pages4
JournalJournal of Immunology
Volume162
Issue number5
StatePublished - Mar 1 1999

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Natural Killer Cells
Phosphotyrosine
Proteins
src-Family Kinases
Genetic Models
Type C Phospholipases
Second Messenger Systems
human LAT protein
Protein-Tyrosine Kinases
Tyrosine
Phosphorylation

ASJC Scopus subject areas

  • Immunology

Cite this

Jevremovic, D., Billadeau, D. D., Schoon, R. A., Dick, C. J., Irvin, B. J., Zhang, W., ... Leibson, P. J. (1999). Cutting edge: A role for the adaptor protein LAT in human NK cell- mediated cytotoxicity. Journal of Immunology, 162(5), 2453-2456.

Cutting edge : A role for the adaptor protein LAT in human NK cell- mediated cytotoxicity. / Jevremovic, Dragan; Billadeau, Daniel D; Schoon, Renee A.; Dick, Christopher J.; Irvin, Brenda J.; Zhang, Weiguo; Samelson, Lawrence E.; Abraham, Robert T.; Leibson, Paul J.

In: Journal of Immunology, Vol. 162, No. 5, 01.03.1999, p. 2453-2456.

Research output: Contribution to journalArticle

Jevremovic, D, Billadeau, DD, Schoon, RA, Dick, CJ, Irvin, BJ, Zhang, W, Samelson, LE, Abraham, RT & Leibson, PJ 1999, 'Cutting edge: A role for the adaptor protein LAT in human NK cell- mediated cytotoxicity', Journal of Immunology, vol. 162, no. 5, pp. 2453-2456.
Jevremovic, Dragan ; Billadeau, Daniel D ; Schoon, Renee A. ; Dick, Christopher J. ; Irvin, Brenda J. ; Zhang, Weiguo ; Samelson, Lawrence E. ; Abraham, Robert T. ; Leibson, Paul J. / Cutting edge : A role for the adaptor protein LAT in human NK cell- mediated cytotoxicity. In: Journal of Immunology. 1999 ; Vol. 162, No. 5. pp. 2453-2456.
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