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Cutting edge: mouse pellino-2 modulates IL-1 and lipopolysaccharide signaling
Kang-Yeol Yu1, Hyung-Joo Kwon, David A M Norman
1Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and Walther Cancer Institute, 1044 West Walnut Street, Indianapolis, IN 46202, USA.
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.
Insights
Mouse pellino-2 is a novel protein involved in embryonic development and adult tissue function. It plays a role in the IL-1/LPS signaling pathway, impacting NF-kappaB activation.
Area of Science:
- Molecular Biology
- Immunology
- Developmental Biology
Background:
- Pellino is a Drosophila protein interacting with the Pelle kinase.
- Mammalian homologs of Pellino exist, but their function remains unclear.
Purpose of the Study:
- To clone, express, and characterize mouse pellino-2.
- To investigate the role of mouse pellino-2 in IL-1/LPS signaling pathways.
Main Methods:
- Cloning and expression analysis of mouse pellino-2.
- Investigating protein-protein interactions using IL-1 stimulation.
- Assessing NF-kappaB activation via reporter assays with antisense constructs.
Main Results:
- Mouse pellino-2 exhibits restricted expression during embryogenesis and in adult tissues.
- IL-1 induces the association of mouse pellino-2 with Pelle-like kinase/IL-1R-associated kinase.
- Ectopic pellino-2 did not activate NF-kappaB, but its antisense construct inhibited IL-1/LPS-induced NF-kappaB activity.
Conclusions:
- Mouse pellino-2 is a tissue-restricted signaling component.
- It links Pelle-like kinase/IL-1R-associated kinase to IL-1/LPS-dependent signaling pathways.