title: Unc119, a novel activator of Lck/Fyn, is essential for T cell activation.
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.
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555, USA.
authors.forename: Magdalena M
authors.initials: MM
authors.lastname: Gorska
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Stafford
authors.forename: Osman
authors.initials: O
authors.lastname: Cen
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Sur
authors.forename: Rafeul
authors.initials: R
authors.lastname: Alam
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008868:Microtubule Proteins; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008868:Microtubule Proteins; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; C402726:Sh2d2a protein, mouse; C489115:Unc119 protein, mouse