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Mitogen-activated protein kinase activity is involved in effector functions triggered by the CD94/NKG2-C NK receptor

M Carretero1, M Llano, F Navarro

  • 1Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.

European Journal of Immunology
|November 9, 2000
PubMed

Insights

The CD94/NKG2C receptor complex on NK cells activates signaling pathways, including mitogen-activated protein kinase (MAPK), leading to tumor cell killing. This pathway is crucial for CD94-mediated TNF-alpha production and cytotoxicity.

Area of Science:

  • Immunology
  • Cellular signaling

Background:

  • CD94/NKG2C is an activating receptor on NK cells.
  • It recognizes the HLA-E molecule.
  • Signal transduction involves DAP12/KARAP.

Purpose of the Study:

  • To investigate the signaling pathways downstream of CD94/NKG2C engagement.
  • To determine the role of MAPK in CD94-mediated functions.
  • To demonstrate the activating function of the CD94/NKG2C-DAP12 complex in a heterologous system.

Main Methods:

  • Engagement of CD94/NKG2C on an NK clone.
  • Inhibition of MAPK pathway using PD098059.
  • Transfection of RBL cells with CD94/NKG2C and DAP12.

Main Results:

  • Receptor engagement induced mitogen-activated protein kinase (MAPK) phosphorylation.
  • MAPK pathway inhibition reduced TNF-alpha production and cytotoxicity.
  • Transfected RBL cells showed calcium mobilization, serotonin release, and MAPK phosphorylation upon receptor cross-linking.

Conclusions:

  • The MAPK pathway is essential for CD94/NKG2C-mediated TNF-alpha production and cytotoxicity.
  • The CD94/NKG2C-DAP12 complex can confer activating functions to heterologous cells.

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