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Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity.

Publication ,  Journal Article
Jevremovic, D; Billadeau, DD; Schoon, RA; Dick, CJ; Irvin, BJ; Zhang, W; Samelson, LE; Abraham, RT; Leibson, PJ
Published in: J Immunol
March 1, 1999

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.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

March 1, 1999

Volume

162

Issue

5

Start / End Page

2453 / 2456

Location

United States

Related Subject Headings

  • Type C Phospholipases
  • Phosphoproteins
  • Membrane Proteins
  • Lymphocyte Activation
  • Killer Cells, Natural
  • Immunology
  • Humans
  • Cytotoxicity, Immunologic
  • Cell Line
  • Carrier Proteins
 

Citation

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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. J Immunol, 162(5), 2453–2456.
Jevremovic, D., D. D. Billadeau, R. A. Schoon, C. J. Dick, B. J. Irvin, W. Zhang, L. E. Samelson, R. T. Abraham, and P. J. Leibson. “Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity.J Immunol 162, no. 5 (March 1, 1999): 2453–56.
Jevremovic D, Billadeau DD, Schoon RA, Dick CJ, Irvin BJ, Zhang W, et al. Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity. J Immunol. 1999 Mar 1;162(5):2453–6.
Jevremovic, D., et al. “Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity.J Immunol, vol. 162, no. 5, Mar. 1999, pp. 2453–56.
Jevremovic D, Billadeau DD, Schoon RA, Dick CJ, Irvin BJ, Zhang W, Samelson LE, Abraham RT, Leibson PJ. Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity. J Immunol. 1999 Mar 1;162(5):2453–2456.

Published In

J Immunol

ISSN

0022-1767

Publication Date

March 1, 1999

Volume

162

Issue

5

Start / End Page

2453 / 2456

Location

United States

Related Subject Headings

  • Type C Phospholipases
  • Phosphoproteins
  • Membrane Proteins
  • Lymphocyte Activation
  • Killer Cells, Natural
  • Immunology
  • Humans
  • Cytotoxicity, Immunologic
  • Cell Line
  • Carrier Proteins