title: Defect of vacuolar protein sorting stimulates proteolytic processing of human urokinase-type plasminogen activator in the yeast Hansenula polymorpha.
abstract: Human urokinase-type plasminogen activator (uPA) is poorly secreted by yeast cells. Here, we have selected Hansenula polymorpha mutants with increased productivity of active extracellular uPA. Several of the obtained mutants also demonstrated a defect of sorting of carboxypeptidase Y to the vacuole and the mutant loci have been identified in six of them. All these mutations damaged genes involved in protein traffic between the Golgi apparatus and the vacuole, namely PEP3, VPS8, VPS10, VPS17, and VPS35. We have shown that inactivation of the VPS10 gene encoding the vacuolar protein sorting receptor does not increase uPA secretion but stimulates its proteolytic processing.
authors.affiliation: Institute of Experimental Cardiology, Cardiology Research Center, 3rd Cherepkovskaya Str. 15A, Moscow 121552, Russia. aga@cardio.ru
authors.forename: Michael
authors.initials: M
authors.lastname: Agaphonov
authors.forename: Nina
authors.initials: N
authors.lastname: Romanova
authors.forename: Sviatoslav
authors.initials: S
authors.lastname: Sokolov
authors.forename: Anna
authors.initials: A
authors.lastname: Iline
authors.forename: Tatyana
authors.initials: T
authors.lastname: Kalebina
authors.forename: Gerd
authors.initials: G
authors.lastname: Gellissen
authors.forename: Michael
authors.initials: M
authors.lastname: Ter-Avanesyan
mesh_terms: D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D006801:Humans; D010843:Pichia / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D010960:Plasminogen Activators / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014617:Vacuoles / Q000201:enzymology
chemical_list: D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator