Unc119, a Novel Activator of Lck/Fyn, Is Essential for T Cell Activation

Magdalena M. Gorska, Susan J. Stafford, Osman Cen, Sanjiv Sur, Rafeul Alam

Research output: Contribution to journalArticle

68 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)369-379
Number of pages11
JournalJournal of Experimental Medicine
Volume199
Issue number3
DOIs
StatePublished - Feb 2 2004

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Keywords

  • IL-2
  • SH3 domain
  • Signal transduction
  • Src kinases
  • T cell antigen receptor

ASJC Scopus subject areas

  • Immunology

Cite this

Gorska, M. M., Stafford, S. J., Cen, O., Sur, S., & Alam, R. (2004). Unc119, a Novel Activator of Lck/Fyn, Is Essential for T Cell Activation. Journal of Experimental Medicine, 199(3), 369-379. https://doi.org/10.1084/jem.