Defect of vacuolar protein sorting stimulates proteolytic processing of human urokinase-type plasminogen activator in the yeast Hansenula polymorpha.
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.
Agaphonov
Michael
M
Institute of Experimental Cardiology, Cardiology Research Center, 3rd Cherepkovskaya Str. 15A, Moscow 121552, Russia. aga@cardio.ru
Romanova
Nina
N
Sokolov
Sviatoslav
S
Iline
Anna
A
Kalebina
Tatyana
T
Gellissen
Gerd
G
Ter-Avanesyan
Michael
M
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
D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator