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Defect of vacuolar protein sorting stimulates proteolytic processing of human urokinase-type plasminogen activator in the yeast Hansenula polymorpha
Article first published online: 9 JAN 2006
FEMS Yeast Research
Volume 5, Issue 11, pages 1029–1035, November 2005
How to Cite
Agaphonov, M., Romanova, N., Sokolov, S., Iline, A., Kalebina, T., Gellissen, G. and Ter-Avanesyan, M. (2005), Defect of vacuolar protein sorting stimulates proteolytic processing of human urokinase-type plasminogen activator in the yeast Hansenula polymorpha. FEMS Yeast Research, 5: 1029–1035. doi: 10.1016/j.femsyr.2005.07.003
- Issue published online: 9 JAN 2006
- Article first published online: 9 JAN 2006
- Received 4 May 2005, Revised 12 July 2005, Accepted 14 July 2005
- Hansenula polymorpha;
- Protein secretion;
- Vacuolar protein sorting;
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.