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

67 Citations (Scopus)

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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src-Family Kinases
T-Cell Antigen Receptor
T-Lymphocytes
Interleukin-2
Cell Proliferation
Ligands

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.

Unc119, a Novel Activator of Lck/Fyn, Is Essential for T Cell Activation. / Gorska, Magdalena M.; Stafford, Susan J.; Cen, Osman; Sur, Sanjiv; Alam, Rafeul.

In: Journal of Experimental Medicine, Vol. 199, No. 3, 02.02.2004, p. 369-379.

Research output: Contribution to journalArticle

Gorska, MM, Stafford, SJ, Cen, O, Sur, S & Alam, R 2004, 'Unc119, a Novel Activator of Lck/Fyn, Is Essential for T Cell Activation', Journal of Experimental Medicine, vol. 199, no. 3, pp. 369-379. https://doi.org/10.1084/jem.
Gorska, Magdalena M. ; Stafford, Susan J. ; Cen, Osman ; Sur, Sanjiv ; Alam, Rafeul. / Unc119, a Novel Activator of Lck/Fyn, Is Essential for T Cell Activation. In: Journal of Experimental Medicine. 2004 ; Vol. 199, No. 3. pp. 369-379.
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