Unc119, a novel activator of Lck/Fyn, is essential for T cell activation.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Carrier Proteins, Cloning, Molecular, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Lymphocyte Activation, Mice, Microtubule Proteins, Receptors, Antigen, T-Cell, Recombinant Proteins, Signal Transduction, T-Lymphocytes, src Homology Domains
Adaptor Proteins, Signal Transducing, Animals, Carrier Proteins, Cloning, Molecular, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Lymphocyte Activation, Mice, Microtubule Proteins, Receptors, Antigen, T-Cell, Recombinant Proteins, Signal Transduction, T-Lymphocytes, src Homology Domains
J. Exp. Med.
Date: Feb. 02, 2004
PubMed ID: 14757743
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