title: A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes.
abstract: Epidermal growth factor receptor (EGFr) is a key mediator of cell communication during animal development and homeostasis. In Drosophila, the signaling event is commonly regulated by the polytopic membrane protein Rhomboid (RHO), which mediates the proteolytic activation of EGFr ligands, allowing the secretion of the active signal. Until very recently, the biochemical function of RHO had remained elusive. It is now believed that Drosophila RHO is the founder member of a previously undescribed family of serine proteases, and that it could be directly responsible for the unusual, intramembranous cleavage of EGFr ligands. Here we show that the function of RHO is conserved in Gram-negative bacteria. AarA, a Providencia stuartii RHO-related protein, is active in Drosophila on the fly EGFr ligands. Vice versa, Drosophila RHO-1 can effectively rescue the bacterium's ability to produce or release the signal that activates density-dependent gene regulation (or quorum sensing). This study provides the first evidence that prokaryotic and eukaryotic RHOs could have a conserved role in cell communication and that their biochemical properties could be more similar than previously anticipated.
authors.affiliation: Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden. marco.gallio@sh.se
authors.forename: Marco
authors.initials: M
authors.lastname: Gallio
authors.forename: Gwen
authors.initials: G
authors.lastname: Sturgill
authors.forename: Philip
authors.initials: P
authors.lastname: Rather
authors.forename: Per
authors.initials: P
authors.lastname: Kylsten
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D011532:Providencia / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; D012097:Repressor Proteins; C081481:Rho protein, Drosophila; C472498:Stet protein, Drosophila; C088713:aarA protein, Providencia stuartii; D066246:ErbB Receptors; D012697:Serine Endopeptidases