PMID- 11729324
OWN - NLM
STAT- MEDLINE
DCOM- 20011231
LR  - 20220310
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 294
IP  - 5548
DP  - 2001 Nov 30
TI  - Regulation of cell survival by secreted proneurotrophins.
PG  - 1945-8
AB  - Neurotrophins are growth factors that promote cell survival, differentiation, and 
      cell death. They are synthesized as proforms that can be cleaved intracellularly 
      to release mature, secreted ligands. Although proneurotrophins have been 
      considered inactive precursors, we show here that the proforms of nerve growth 
      factor (NGF) and the proforms of brain derived neurotrophic factor (BDNF) are 
      secreted and cleaved extracellularly by the serine protease plasmin and by 
      selective matrix metalloproteinases (MMPs). ProNGF is a high-affinity ligand for 
      p75(NTR) with high affinity and induced p75NTR-dependent apoptosis in cultured 
      neurons with minimal activation of TrkA-mediated differentiation or survival. The 
      biological action of neurotrophins is thus regulated by proteolytic cleavage, 
      with proforms preferentially activating p75NTR to mediate apoptosis and mature 
      forms activating Trk receptors to promote survival.
FAU - Lee, R
AU  - Lee R
AD  - Division of Hematology, Department of Medicine, Weill Medical College of Cornell 
      University, 1300 York Avenue, New York, NY 10021, USA.
FAU - Kermani, P
AU  - Kermani P
FAU - Teng, K K
AU  - Teng KK
FAU - Hempstead, B L
AU  - Hempstead BL
LA  - eng
GR  - NS30687/NS/NINDS NIH HHS/United States
GR  - T32 EY07138/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Protein Precursors)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 3.4.21.- (Subtilisins)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - EC 3.4.21.75 (Furin)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Brain-Derived Neurotrophic Factor/chemistry/metabolism/pharmacology
MH  - Cell Death/drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - *Cell Survival/drug effects
MH  - Fibrinolysin/metabolism
MH  - Furin
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Matrix Metalloproteinases/metabolism
MH  - Mice
MH  - Nerve Growth Factor/chemistry/metabolism/pharmacology
MH  - Nerve Growth Factors/chemistry/*metabolism/pharmacology
MH  - Neurons/cytology/drug effects
MH  - Phosphorylation/drug effects
MH  - Protein Precursors/chemistry/*metabolism/pharmacology
MH  - Protein Processing, Post-Translational
MH  - Rats
MH  - Receptor, Nerve Growth Factor
MH  - Receptor, trkA/metabolism
MH  - Receptors, Nerve Growth Factor/metabolism
MH  - Subtilisins/metabolism
EDAT- 2001/12/01 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/12/01 10:00
PHST- 2001/12/01 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/12/01 10:00 [entrez]
AID - 294/5548/1945 [pii]
AID - 10.1126/science.1065057 [doi]
PST - ppublish
SO  - Science. 2001 Nov 30;294(5548):1945-8. doi: 10.1126/science.1065057.