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Cutting edge: functional role for proline-rich tyrosine kinase 2 in NK cell-mediated natural cytotoxicity

A Gismondi1, J Jacobelli, F Mainiero

  • 1Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome "La Sapienza"; and Mediterranean Institute of Neuroscience, Neuromed, Pozzilli, Italy.

Journal of Immunology (Baltimore, Md. : 1950)
|February 29, 2000
PubMed

Insights

Proline-rich tyrosine kinase 2 (Pyk2) is activated during natural killer (NK) cell interactions with target cells. Pyk2 plays a role in natural, but not antibody-mediated, NK cell cytotoxicity by regulating extracellular signal-regulated kinase activation.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Protein tyrosine kinase activation is crucial for natural killer (NK) cell cytolytic function.
  • The role of proline-rich tyrosine kinase 2 (Pyk2) in NK cell cytotoxicity is not well understood.

Purpose of the Study:

  • To investigate the role of Pyk2 in NK cell-mediated cytotoxicity.
  • To determine the signaling pathways regulated by Pyk2 in NK cells.

Main Methods:

  • NK cell binding assays with target cells.
  • Analysis of Pyk2 phosphorylation and activation.
  • Functional assays using kinase-dead Pyk2 mutants.
  • Investigation of extracellular signal-regulated kinase (ERK) activation.

Main Results:

  • Pyk2 phosphorylation and activation were induced upon NK cell binding to target cells and beta2 integrin ligation.
  • Pyk2 was not activated by CD16 stimulation (mAb or antibody-coated cells).
  • Kinase-dead Pyk2 impaired natural cytotoxicity but not antibody-mediated cytotoxicity.
  • Pyk2 is involved in beta2 integrin-triggered ERK activation.

Conclusions:

  • Pyk2 plays a significant role in natural NK cell cytotoxicity.
  • Pyk2 regulates NK cell cytotoxicity through the beta2 integrin-dependent ERK signaling pathway.

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