Cutting edge: mouse pellino-2 modulates IL-1 and lipopolysaccharide signaling.
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.
Yu
Kang-Yeol
KY
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and Walther Cancer Institute, 1044 West Walnut Street, Indianapolis, IN 46202, USA.
Kwon
Hyung-Joo
HJ
Norman
David A M
DA
Vig
Eva
E
Goebl
Mark G
MG
Harrington
Maureen A
MA
D000818:Animals; D015152:Blotting, Northern; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000502:physiology; D053592:Interleukin-1 Receptor-Associated Kinases; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051193:Toll-Like Receptors; D044767:Ubiquitin-Protein Ligases
D029721:Drosophila Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; C485961:Peli2 protein, mouse; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; C485959:PELI1 protein, human; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C418046:Peli1 protein, mouse