Abstract
Pellino is a Drosophila protein originally isolated in a two-hybrid screen for proteins interacting with the serine/threonine kinase, pelle. Although mammalian homologs have been identified in mouse and man, the function of pellino is as yet unknown. In this study, the cloning, expression pattern, and a preliminary characterization of mouse pellino-2 is described. These studies reveal that mouse pellino-2 is expressed during embryogenesis and in a tissue-restricted manner in the adult. IL-1 induces the association of mouse pellino-2 with the mouse pelle-like kinase/IL-1R-associated kinase protein, a mammalian homolog of pelle. Ectopic pellino-2 expression did not result in NF-kappaB activation. However, ectopic expression of a mouse pellino-2 antisense construct inhibited IL-1 or LPS-induced activation of NF-kappaB-dependent IL-8 promoter activity. Our data reveal that mouse pellino-2 is a tissue-restricted component of a signaling pathway that couples the mouse pelle-like kinase/IL-1R-associated kinase protein to IL-1- or LPS-dependent signaling.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Blotting, Northern
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Line
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Cloning, Molecular
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Drosophila Proteins*
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Gene Expression / immunology
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Humans
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Interleukin-1 / metabolism*
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Interleukin-1 / physiology
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Interleukin-1 Receptor-Associated Kinases
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Lipopolysaccharides / pharmacology*
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C3H
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Nuclear Proteins / physiology*
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Protein Kinases / metabolism
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Receptors, Cell Surface / physiology
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Receptors, Interleukin-1 / metabolism
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Receptors, Interleukin-1 / physiology
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Toll-Like Receptors
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Ubiquitin-Protein Ligases
Substances
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Drosophila Proteins
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Interleukin-1
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Lipopolysaccharides
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Membrane Glycoproteins
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Nuclear Proteins
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Peli2 protein, mouse
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Receptors, Cell Surface
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Receptors, Interleukin-1
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Toll-Like Receptors
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PELI1 protein, human
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Ubiquitin-Protein Ligases
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Protein Kinases
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Interleukin-1 Receptor-Associated Kinases
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Irak1 protein, mouse
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Calcium-Calmodulin-Dependent Protein Kinases
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Peli1 protein, mouse