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. Epub 2004 Jan 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Cloning, Molecular
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Lymphocyte Activation / immunology*
  • Mice
  • Microtubule Proteins
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Proteins / immunology
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*
  • src Homology Domains

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Microtubule Proteins
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • Sh2d2a protein, mouse
  • Unc119 protein, mouse