title: Upd3--an ancestor of the four-helix bundle cytokines.
abstract: The unpaired-like protein 3 (Upd3) is one of the three cytokines of Drosophila melanogaster supposed to activate the JAK/STAT signaling pathway (Janus tyrosine kinases/signal transducer and activator of transcription). This activation occurs via the type-I cytokine receptor domeless, an orthologue of gp130, the common signal transducer of all four-helix bundle interleukin-6 (IL-6) type cytokines. Both receptors are known to exist as preformed dimers in the plasma membrane and initiate the acute-phase response. These facts indicate an evolutionary relation between vertebrate IL-6 and the Drosophila protein Upd3. Here we presented data which strengthen this notion. Upd3 was recombinantly expressed, a renaturation and purification protocol was established which allows to obtain high amounts of biological active protein. This protein is, like human IL-6, a monomeric-α helical cytokine, implicating that Upd3 is an "ancestor" of the four-helix bundle cytokines.
authors.affiliation: Biochemisches Institut der Christian-Albrechts-Universität Kiel, Olshausenstr. 40, 24118 Kiel, Germany. moldefest@biochem.uni-kiel.de
authors.forename: Mirja
authors.initials: M
authors.lastname: Oldefest
authors.forename: Jana
authors.initials: J
authors.lastname: Nowinski
authors.forename: Chien-Wen
authors.initials: CW
authors.lastname: Hung
authors.forename: Denis
authors.initials: D
authors.lastname: Neelsen
authors.forename: Ahmad
authors.initials: A
authors.lastname: Trad
authors.forename: Andreas
authors.initials: A
authors.lastname: Tholey
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
authors.forename: Inken
authors.initials: I
authors.lastname: Lorenzen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000737:chemistry*; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D029721:Drosophila Proteins / Q000737:chemistry*; D004331:Drosophila melanogaster / Q000737:chemistry*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D004220:Disulfides; D029721:Drosophila Proteins; D015850:Interleukin-6; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; C558732:Upd3 protein, Drosophila