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Association of DAP12 with activating CD94/NKG2C NK cell receptors

L L Lanier1, B Corliss, J Wu

  • 1DNAX Research Institute of Molecular and Cellular Biology, Immunobiology Department, Palo Alto, California 94304, USA. lanier@dnax.org

Immunity
|July 9, 1998
PubMed

Insights

Activating NK cell receptors like CD94/NKG2C associate with DAP12 to enable cellular activation. Charged residues in their transmembrane domains are crucial for this essential NK cell receptor assembly.

Area of Science:

  • Immunology
  • Cellular Biology
  • Molecular Biology

Background:

  • Inhibitory NK cell receptors utilize immunoreceptor tyrosine-based inhibitory motifs for signaling.
  • Activating NK cell receptors lack intrinsic signaling sequences, necessitating co-receptors for function.

Purpose of the Study:

  • To elucidate the molecular mechanism of activating NK cell receptor assembly and function.
  • To identify the signaling partners and structural requirements for CD94/NKG2C surface expression and activation.

Main Methods:

  • Investigated the association of CD94/NKG2C with DAP12.
  • Analyzed the role of transmembrane domain residues in receptor complex formation.
  • Assessed cell surface expression of CD94/NKG2C in the presence of DAP12.

Main Results:

  • CD94/NKG2C, an activating NK cell receptor, noncovalently associates with DAP12, a signaling adaptor protein.
  • Efficient surface expression of CD94/NKG2C is dependent on the presence of DAP12.
  • Specific charged residues within the transmembrane domains of both DAP12 and NKG2C are essential for their stable interaction.

Conclusions:

  • DAP12 is critical for the surface expression and function of the activating NK cell receptor CD94/NKG2C.
  • The interaction between CD94/NKG2C and DAP12, mediated by transmembrane charged residues, provides a molecular basis for NK cell activation signaling.
  • This study clarifies the assembly mechanism of activating NK cell receptors, complementing the understanding of inhibitory receptor signaling.

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