title: Negative regulation of prophenoloxidase (proPO) activation by a clip-domain serine proteinase homolog (SPH) from endoparasitoid venom.
abstract: Most parasitic wasps inject maternal factors into the host hemocoel to suppress the host immune system and ensure successful development of their progeny. Melanization is one of the insect defence mechanisms against intruding pathogens or parasites. We previously isolated from the venom of Cotesia rubecula a 50 kDa protein that blocked melanization in the hemolymph of its host, Pieris rapae [Insect Biochem. Mol. Biol. 33 (2003) 1017]. This protein, designated Vn50, is a serine proteinase homolog (SPH) containing an amino-terminal clip domain. In this work, we demonstrated that recombinant Vn50 bound P. rapae hemolymph components that were recognized by antisera to Tenebrio molitor prophenoloxidase (proPO) and Manduca sexta proPO-activating proteinase (PAP). Vn50 is stable in the host hemolymph-it remained intact for at least 72 h after parasitization. Using M. sexta as a model system, we found that Vn50 efficiently down-regulated proPO activation mediated by M. sexta PAP-1, SPH-1, and SPH-2. Vn50 did not inhibit active phenoloxidase (PO) or PAP-1, but it significantly reduced the proteolysis of proPO. If recombinant Vn50 binds P. rapae proPO and PAP (as suggested by the antibody reactions), it is likely that the molecular interactions among M. sexta proPO, PAP-1, and SPHs were impaired by this venom protein. A similar strategy might be employed by C. rubecula to negatively impact the proPO activation reaction in its natural host.
authors.affiliation: Insect Molecular Biology Laboratory, Plant and Pest Science, Waite Campus, University of Adelaide, Glen Osmond, SA 5064, Australia.
authors.forename: Guangmei
authors.initials: G
authors.lastname: Zhang
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Lu
authors.forename: Haobo
authors.initials: H
authors.lastname: Jiang
authors.forename: Sassan
authors.initials: S
authors.lastname: Asgari
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D002080:Butterflies / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology; D020134:Catalytic Domain; D004156:Catechol Oxidase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004355:Drug Stability; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism*; D006458:Hemolymph / Q000187:drug effects / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D018402:Manduca / Q000201:enzymology; D000073718:Pancreatitis-Associated Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014862:Wasp Venoms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014863:Wasps / Q000201:enzymology
chemical_list: D004792:Enzyme Precursors; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D011994:Recombinant Proteins; D014862:Wasp Venoms; C038451:pro-phenoloxidase; D004156:Catechol Oxidase; D012697:Serine Endopeptidases; C115269:pro-phenol oxidase activating proteinase; D000581:Amidohydrolases