Open AccessDefect of vacuolar protein sorting stimulates proteolytic processing of human urokinase‐type plasminogen activator in the yeast Hansenula polymorpha
Author(s) -
Agaphonov Michael,
Romanova Nina,
Sokolov Sviatoslav,
Iline Anna,
Kalebina Tatyana,
Gellissen Gerd,
TerAvanesyan Michael
Publication year - 2005
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1016/j.femsyr.2005.07.003
Subject(s) - biology , vacuolar protein sorting , mutant , vacuole , plasminogen activator , secretion , microbiology and biotechnology , activator (genetics) , yeast , gene , biochemistry , genetics , cytoplasm
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.