Tube Is an IRAK-4 homolog in a Toll pathway adapted for development and immunity.
Acting through the Pelle and IRAK family of protein kinases, Toll receptors mediate innate immune responses in animals ranging from insects to humans. In flies, the Toll pathway also functions in patterning of the syncytial embryo and requires Tube, a Drosophila -specific adaptor protein lacking a catalytic domain. Here we provide evidence that the Tube, Pelle, and IRAK proteins originated from a common ancestral gene. Following gene duplication, IRAK-4, Tube-like kinases, and Tube diverged from IRAK-1, Pelle, and related kinases. Remarkably, the function of Tube and Pelle in Drosophila embryos can be reconstituted in a chimera modeled on the predicted progenitor gene. In addition, a divergent property of downstream transcription factors was correlated with developmental function. Together, these studies reveal previously unrecognized parallels in Toll signaling in fly and human innate immunity and shed light on the evolution of pathway organization and function.
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Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0349, USA.
Sun
Huaiyu
H
Wasserman
Steven A
SA
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D011993:Recombinant Fusion Proteins; D051193:Toll-Like Receptors; D014157:Transcription Factors; C084727:tub protein, Drosophila; C079896:pll protein, Drosophila; D053592:Interleukin-1 Receptor-Associated Kinases; D017346:Protein Serine-Threonine Kinases