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Src-dependent Syk activation controls CD69-mediated signaling and function on human NK cells.
Simona Pisegna1, Alessandra Zingoni, Gianluca Pirozzi
1Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci Bolognetti, University La Sapienza, Rome, Italy.
Journal of Immunology (Baltimore, Md. : 1950)
|June 22, 2002
Summary
CD69 engagement activates the tyrosine kinase Syk, not ZAP70, in human NK cells. This pathway, involving Src family kinases, controls CD69-mediated cytotoxicity.
Area of Science:
- Immunology
- Cell Signaling
Background:
- CD69 is a C-type lectin receptor on activated NK cells that triggers cytotoxic activity.
- The precise signaling pathways downstream of CD69 remain incompletely understood.
Purpose of the Study:
- To elucidate the proximal signaling events initiated by CD69 engagement in human NK cells.
- To identify the key kinases and downstream effectors involved in CD69-mediated cytotoxicity.
Main Methods:
- Utilized IL-2-activated human NK cells and an RBL transfectant clone expressing CD69.
- Investigated tyrosine kinase activation (Syk, ZAP70, Src family kinases) upon CD69 cross-linking.
- Assessed activation of phospholipase Cgamma2 and Vav1, and measured CD69-triggered cytotoxicity.
Main Results:
- CD69 engagement rapidly and selectively activated Syk, but not ZAP70.
- Src family kinases, including Lck, were required for CD69-induced Syk activation.
- Syk and Src family kinases mediated CD69-triggered phosphorylation and activation of phospholipase Cgamma2 and Vav1, leading to cytotoxicity.
Conclusions:
- CD69 functionally couples to Src family tyrosine kinases, initiating Syk activation.
- This signaling cascade is crucial for regulating CD69-triggered cytotoxicity in human NK cells.