Abstract

Furin is a membrane-localized endoprotease that cleaves a number of biologically important molecules as part of their normal biosynthesis and processing. Cleavage takes place in the TGN and also in endosomes and at the cell surface. The applicant has invested a great deal of effort in analyzing the role of specific cytoplasmic domain residues in facilitating the endocytosis and TGN recycling of this important processing protease. The goals of this application are to: (1) use quantitative assays of furin trafficking and explore the effects of specific cytosolic tail mutations and phosphorylation/dephosphorylation on these steps; (2) characterize a tautomycin sensitive furin phosphatase that seems to play a role in early endosome export of the protein; and (3) characterize the role of actin binding protein-ABP-280 on furin cycling.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK044629-05A1
Application #
2016481
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Haft, Carol Renfrew
Project Start
1992-03-01
Project End
2000-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Type
Organized Research Units
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

Dillon, Stephanie L; Williamson, Danielle M; Elferich, Johannes et al. (2012) Propeptides are sufficient to regulate organelle-specific pH-dependent activation of furin and proprotein convertase 1/3. J Mol Biol 423:47-62
Thomas, Gary (2002) Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol 3:753-66
Crump, C M; Xiang, Y; Thomas, L et al. (2001) PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic. EMBO J 20:2191-201
Xiang, Y; Molloy, S S; Thomas, L et al. (2000) The PC6B cytoplasmic domain contains two acidic clusters that direct sorting to distinct trans-Golgi network/endosomal compartments. Mol Biol Cell 11:1257-73
Molloy, S S; Anderson, E D; Jean, F et al. (1999) Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis. Trends Cell Biol 9:28-35
Molloy, S S; Thomas, L; Kamibayashi, C et al. (1998) Regulation of endosome sorting by a specific PP2A isoform. J Cell Biol 142:1399-411
Jean, F; Stella, K; Thomas, L et al. (1998) alpha1-Antitrypsin Portland, a bioengineered serpin highly selective for furin: application as an antipathogenic agent. Proc Natl Acad Sci U S A 95:7293-8
Wan, L; Molloy, S S; Thomas, L et al. (1998) PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization. Cell 94:205-16
Cui, Y; Jean, F; Thomas, G et al. (1998) BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development. EMBO J 17:4735-43
Anderson, E D; VanSlyke, J K; Thulin, C D et al. (1997) Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage. EMBO J 16:1508-18

Showing the most recent 10 out of 23 publications