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Identification of UNC119 as a Novel Activator of
SRC-type Tyrosine Kinases*
Osman
Cen§¶,
Magdalena M.
Gorska,
Susan J.
Stafford,
Sanjiv
Sur, and
Rafeul
Alam§
From the Division of Allergy and Immunology,
NIAID, National Institutes of Health Asthma and Allergic Diseases
Research Center, Department of Internal Medicine, and the
§ Department of Microbiology and Immunology, University of
Texas Medical Branch, Galveston, Texas 77555
Lyn, an Src-type tyrosine kinase, is associated
with the interleukin (IL)-5 receptor in eosinophils. The mechanism of
itsactivation is unknown. Through yeast two-hybrid screening we havecloned and characterized a new signaling molecule, Unc119, thatassociates with IL-5R and Src family tyrosine kinases. Unc119induces the catalytic activity of these kinases through interactionwith Src homology 2 and 3 domains. IL-5 stimulation of eosinophilsincreases Unc119 association with Lyn and induces its catalyticactivity. Lyn is important for eosinophil survival. Eosinophilsthat
are transduced with Unc119 have increased Lyn activity anddemonstrate
prolonged survival in the absence of IL-5. Inhibitionof Unc119
down-regulates eosinophil survival. To our knowledgeUnc119 is the
first receptor-associated activator of Src familytyrosinekinases.
Uncoordinated 119 Preferentially Induces Th2 Differentiation and Promotes the Development of Asthma.
M. M. Gorska, N. Goplen, Q. Liang, and R. Alam (2010)
J. Immunol.
184, 4488-4496
|Abstract »|Full Text »|PDF »
Uncoordinated 119 Protein Controls Trafficking of Lck via the Rab11 Endosome and Is Critical for Immunological Synapse Formation.
M. M. Gorska, Q. Liang, Z. Karim, and R. Alam (2009)
J. Immunol.
183, 1675-1684
|Abstract »|Full Text »|PDF »
RIBEYE Recruits Munc119, a Mammalian Ortholog of the Caenorhabditis elegans Protein unc119, to Synaptic Ribbons of Photoreceptor Synapses.
K. Alpadi, V. G. Magupalli, S. Kappel, L. Koblitz, K. Schwarz, G. M. Seigel, C.-H. Sung, and F. Schmitz (2008)
J. Biol. Chem.
283, 26461-26467
|Abstract »|Full Text »|PDF »
Interaction and Colocalization of CaBP4 and Unc119 (MRG4) in Photoreceptors.
Unc119 Regulates Myofibroblast Differentiation through the Activation of Fyn and the p38 MAPK Pathway.
R. Vepachedu, M. M. Gorska, N. Singhania, G. P. Cosgrove, K. K. Brown, and R. Alam (2007)
J. Immunol.
179, 682-690
|Abstract »|Full Text »|PDF »
The Membrane-proximal Portion of CD3 {epsilon} Associates with the Serine/Threonine Kinase GRK2.
L. M. DeFord-Watts, J. A. Young, L. A. Pitcher, and N. S. C. van Oers (2007)
J. Biol. Chem.
282, 16126-16134
|Abstract »|Full Text »|PDF »
Differential Regulation of Interleukin 5-stimulated Signaling Pathways by Dynamin.
M. M. Gorska, O. Cen, Q. Liang, S. J. Stafford, and R. Alam (2006)
J. Biol. Chem.
281, 14429-14439
|Abstract »|Full Text »|PDF »
Normal T-Cell Development and Immune Functions in TRIM-Deficient Mice.
U. Kolsch, B. Arndt, D. Reinhold, J. A. Lindquist, N. Juling, S. Kliche, K. Pfeffer, E. Bruyns, B. Schraven, and L. Simeoni (2006)
Mol. Cell. Biol.
26, 3639-3648
|Abstract »|Full Text »|PDF »
Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor {zeta} chain ITAMs and their tyrosine residues.
W.-J. Chae, H.-K. Lee, J.-H. Han, S.-W. V. Kim, A. L.M. Bothwell, T. Morio, and S.-K. Lee (2004)
Int. Immunol.
16, 1225-1236
|Abstract »|Full Text »|PDF »
Unc119, a Novel Activator of Lck/Fyn, Is Essential for T Cell Activation.
M. M. Gorska, S. J. Stafford, O. Cen, S. Sur, and R. Alam (2004)
J. Exp. Med.
199, 369-379
|Abstract »|Full Text »|PDF »
§¶,
and Src family tyrosine kinases. Unc119 induces the catalytic activity of these kinases through interaction with Src homology 2 and 3 domains. IL-5 stimulation of eosinophils increases Unc119 association with Lyn and induces its catalytic activity. Lyn is important for eosinophil survival. Eosinophils that
are transduced with Unc119 have increased Lyn activity and demonstrate
prolonged survival in the absence of IL-5. Inhibition of Unc119
down-regulates eosinophil survival. To our knowledge Unc119 is the
first receptor-associated activator of Src family tyrosine kinases.
