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J. Biol. Chem. 278 (10): 8837-8845

© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification of UNC119 as a Novel Activator of SRC-type Tyrosine Kinases*

Osman CenDagger §, Magdalena M. GorskaDagger , Susan J. StaffordDagger , Sanjiv SurDagger , and Rafeul AlamDagger §||

From the Dagger  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 its activation is unknown. Through yeast two-hybrid screening we have cloned and characterized a new signaling molecule, Unc119, that associates with IL-5Ralpha 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.

* This work was supported in part by National Institutes of Health Grants AI PO1 46004, ES06676, and AI50179, the John Sealy Memorial Fund, and the McLaughlin Fellowship Fund.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported in part by Harran University, SanliUrfa, Turkey.

|| To whom correspondence should be addressed: National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206. E-mail:

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

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