Pellino2 activates the mitogen activated protein kinase pathway.
Engagement of the interleukin-1 (IL1) and Toll receptors, which are part of the innate immune system, facilitates activation of the transcription factors NF-kappaB, Elk-1 and AP-1. Pellino1 and Pellino2 have recently been shown to be intermediates in the pathway leading to activation of NF-kappaB. Here we demonstrate for the first time that human Pellino2 interacts with TRAF6 (tumor necrosis factor receptor associated factor 6) and that both Pellino1 and Pellino2 also interact with TAK1 (transforming growth factor-beta activated kinase 1). We also show that Pellino2, but not Pellino1, can activate the mitogen activated protein kinase pathway leading to activation of AP-1 and Elk-1. These observations suggest a role for the Pellino proteins in the IL1/Toll signaling cascades as scaffold proteins that may regulate signaling branch-points.
Jensen
Liselotte E
LE
Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104-6084, USA. jensen@pharm.med.upenn.edu
Whitehead
Alexander S
AS
D002460:Cell Line; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D017930:Genes, Reporter; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000201:enzymology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D050807:ets-Domain Protein Elk-1; D000099151:MAP Kinase Kinase Kinase 7
D004268:DNA-Binding Proteins; D020930:MAP Kinase Kinase Kinases; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D048029:TNF Receptor-Associated Factor 6; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D050807:ets-Domain Protein Elk-1; D000099151:MAP Kinase Kinase Kinase 7; C494112:ELK1 protein, human; C485959:PELI1 protein, human