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A critical role for p59(fyn) in CD2-based signal transduction
I Fukai1, R E Hussey, R Sunder-Plassmann
1Laboratory of Immunobiology and Department of Cancer Immunology/AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
European Journal of Immunology
|November 28, 2000
Summary
The protein tyrosine kinase p59-fyn is crucial for CD2-mediated T cell activation, regulating calcium mobilization and proliferation. Its absence impairs CD2 signaling but not TCR signaling in T lymphocytes.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- T cell receptor (TCR) signaling relies on p56-lck, but the role of other src-family kinases in CD2 signaling is less understood.
- p59-fyn is a src-family protein tyrosine kinase (PTK) present in T lymphocytes.
Purpose of the Study:
- To investigate the role of p59-fyn in CD2-mediated T cell activation.
- To determine if p59-fyn is an essential upstream component of the CD2 signaling pathway.
Main Methods:
- Generated human CD2 transgenic fyn(+/+) and fyn(-/-) mice.
- Analyzed CD2-triggered calcium mobilization, MAPK activation, and cellular proliferation.
- Assessed phosphorylation and catalytic activity of downstream signaling molecules.
Main Results:
- p59-fyn deficiency markedly reduced CD2-initiated calcium mobilization, MAPK activation, and proliferation, while TCR-triggered proliferation remained unaffected.
- Identified several p59-fyn-regulated CD2 pathway components, including PLC-gamma1, Vav, PKC-theta, Dok, FAK, and Pyk2.
- Demonstrated that p59-fyn is required for CD2-dependent Dok tyrosine phosphorylation and influences T cell adhesion via FAK and Pyk2.
Conclusions:
- p59-fyn is a key PTK in the CD2-mediated activation of mature T lymphocytes.
- p59-fyn plays a critical role in regulating downstream signaling events initiated by CD2 clustering.
- These findings highlight p59-fyn's importance in T cell adhesion and activation pathways.