PMID- 18291105
OWN - NLM
STAT- MEDLINE
DCOM- 20080513
LR  - 20091119
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 582
IP  - 6
DP  - 2008 Mar 19
TI  - Activation of pro-BDNF by the pericellular serine protease plasmin.
PG  - 907-10
LID - 10.1016/j.febslet.2008.02.026 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is secreted as either a mature 
      furin-processed form or an unprocessed pro-form. Here, we characterise the 
      extracellular processing of pro-BDNF by the serine protease plasmin. Using 
      recombinant BDNF, maintained in the pro-form by site-directed mutagenesis or 
      inhibition of furin, we demonstrate that plasmin (but not related proteases) is a 
      specific and efficient activator of pro-BDNF. The proteolytic cleavage site is 
      identified as Arg125-Val, within the consensus furin-cleavage motif (RVRR), 
      generating an active form that stimulated neurite outgrowth on TrkB-transfected 
      PC12 cells. Furthermore, we demonstrate that this processing can also occur in 
      the pericellular environment by the action of cell-associated plasminogen 
      activators.
FAU - Gray, Kelly
AU  - Gray K
AD  - School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
FAU - Ellis, Vincent
AU  - Ellis V
LA  - eng
GR  - FS/03/067/British Heart Foundation/United Kingdom
GR  - FS/1999073/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080220
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Precursors)
RN  - 0 (Recombinant Proteins)
RN  - 0 (brain-derived neurotrophic factor precursor)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - EC 3.4.21.75 (Furin)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/chemistry/genetics/*metabolism
MH  - Cell Membrane/metabolism
MH  - Fibrinolysin/chemistry/*metabolism
MH  - Furin/antagonists & inhibitors/chemistry
MH  - Humans
MH  - Male
MH  - Mutagenesis, Site-Directed
MH  - Neurites/drug effects/physiology
MH  - PC12 Cells
MH  - Protein Precursors/chemistry/genetics/*metabolism
MH  - Rats
MH  - Receptor, trkB/agonists/genetics/metabolism
MH  - Recombinant Proteins/chemistry/genetics/metabolism
EDAT- 2008/02/23 09:00
MHDA- 2008/05/14 09:00
CRDT- 2008/02/23 09:00
PHST- 2008/01/24 00:00 [received]
PHST- 2008/02/08 00:00 [revised]
PHST- 2008/02/11 00:00 [accepted]
PHST- 2008/02/23 09:00 [pubmed]
PHST- 2008/05/14 09:00 [medline]
PHST- 2008/02/23 09:00 [entrez]
AID - S0014-5793(08)00131-2 [pii]
AID - 10.1016/j.febslet.2008.02.026 [doi]
PST - ppublish
SO  - FEBS Lett. 2008 Mar 19;582(6):907-10. doi: 10.1016/j.febslet.2008.02.026. Epub 
      2008 Feb 20.