The Journal of Experimental Medicine
StemCell Technologies
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 26 January 2004 doi:10.1084/jem. 20030589
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 3, 369-379
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gorska, M. M.
Right arrow Articles by Alam, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gorska, M. M.
Right arrow Articles by Alam, R.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*Nucleotide
*OMIM*Protein
*UniGene
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Unc119, a Novel Activator of Lck/Fyn, Is Essential for T Cell Activation

Magdalena M. Gorska1,2, Susan J. Stafford1, Osman Cen1, Sanjiv Sur1, and Rafeul Alam1,2

1 The Division of Allergy and Immunology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555
2 The Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206

Address correspondence to Rafeul Alam, Dept. of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. Phone: 303-270-2907; Fax: 303-398-1225; email: alamr{at}njc.org

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.

Key Words: signal transduction • Src kinases • SH3 domain • T cell antigen receptor • IL-2

The online version of this article includes supplemental material.

Abbreviations used in this paper: GFP, green fluorescent protein; GST, glutathione S-transferase; HRG4, human retinal gene 4; SH, Src homology; Unc119, Uncoordinated 119.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS