Unc119, a novel activator of Lck/Fyn, is essential for T cell activation.
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Gorska MM, Stafford SJ, Cen O, Sur S, Alam R
Unc119, a novel activator of Lck/Fyn, is essential for T cell activation.
J Exp Med. 2004 Feb 2;199(3):369-79. Epub 2004 Jan 23.
- PubMed ID
- 14757743 [ View in PubMed]
- Abstract
The first step in T cell receptor for antigen (TCR) signaling is the activation of the receptor-bound Src kinases, Lck and Fyn. The exact mechanism of this process is unknown. Here, we report that the novel Src homology (SH) 3/SH2 ligand-Uncoordinated 119 (Unc119) associates with CD3 and CD4, and activates Lck and Fyn. Unc119 overexpression increases Lck/Fyn activity in T cells. In Unc119-deficient T cells, Lck/Fyn activity is dramatically reduced with concomitant decrease in interleukin 2 production and cellular proliferation. Reconstitution of cells with Unc119 reverses the signaling and functional outcome. Thus, Unc119 is a receptor-associated activator of Src-type kinases. It provides a novel mechanism of signal generation in the TCR complex.