Identification of UNC119 as a novel activator of SRC-type tyrosine kinases.
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.
Cen
Osman
O
Division of Allergy and Immunology, NIAID, National Institutes of Health Asthma and Allergic Diseases Research Center, Bethesda, Maryland 20892, USA.
Gorska
Magdalena M
MM
Stafford
Susan J
SJ
Sur
Sanjiv
S
Alam
Rafeul
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D017931:DNA Primers; D004789:Enzyme Activation; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D018123:Receptors, Interleukin / Q000378:metabolism / Q000502:physiology; D053649:Receptors, Interleukin-5; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; C098176:UNC-119 protein, C elegans; D019061:src-Family Kinases