Unc119, a novel activator of Lck/Fyn, is essential for T cell activation
- J Exp Med. 2004 Feb 2;199(3):369-79. doi: 10.1084/jem.20030589.
- 1. Division of Allergy and Immunology, Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555, USA.
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.