PMID- 10722747
OWN - NLM
STAT- MEDLINE
DCOM- 20000427
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 12
DP  - 2000 Mar 24
TI  - Down-regulation of the neurotrophin receptor TrkB following ligand binding. 
      Evidence for an involvement of the proteasome and differential regulation of TrkA 
      and TrkB.
PG  - 8982-90
AB  - This study examines the mechanisms by which the tyrosine kinase receptor TrkB is 
      down-regulated following binding of brain-derived neurotrophic factor (BDNF). In 
      primary cultures of cerebellar granule neurons, BDNF-induced reduction of TrkB 
      receptors was largely prevented by the addition of specific proteasome 
      inhibitors. HN10 cells, a neuronal cell line that can be readily transfected, 
      also showed a marked down-regulation of cell surface TrkB following BDNF 
      exposure. In addition, we observed that prolonged exposure to nerve growth factor 
      of TrkA-transfected cells did not lead to the down-regulation seen with BDNF and 
      TrkB. TrkA and TrkB chimeric molecules were therefore expressed in HN10 cells and 
      tested for ligand-induced regulation. These experiments led to the conclusion 
      that the motives responsible for down-regulation are contained in the cytoplasmic 
      domain of TrkB, and a short sequence in the juxtamembrane domain of TrkB was 
      identified that confers nerve growth factor-induced down-regulation when inserted 
      into TrkA.
FAU - Sommerfeld, M T
AU  - Sommerfeld MT
AD  - Max-Planck Institute of Neurobiology, Department of Neurobiochemistry, Am 
      Klopferspitz 18A, 82152 Planegg-Martinsried, Germany.
FAU - Schweigreiter, R
AU  - Schweigreiter R
FAU - Barde, Y A
AU  - Barde YA
FAU - Hoppe, E
AU  - Hoppe E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Ligands)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (Receptor, trkC)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cerebellum/cytology
MH  - Cysteine Endopeptidases/*metabolism
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - *Down-Regulation
MH  - Ligands
MH  - Multienzyme Complexes/*metabolism
MH  - Mutation
MH  - Nerve Growth Factor/metabolism
MH  - Neurons/*physiology
MH  - Proteasome Endopeptidase Complex
MH  - Protein Binding
MH  - Rats
MH  - Receptor, trkA/metabolism
MH  - Receptor, trkB/biosynthesis/*metabolism
MH  - Receptor, trkC/metabolism
MH  - Recombinant Fusion Proteins/metabolism
EDAT- 2000/03/18 09:00
MHDA- 2000/04/29 09:00
CRDT- 2000/03/18 09:00
PHST- 2000/03/18 09:00 [pubmed]
PHST- 2000/04/29 09:00 [medline]
PHST- 2000/03/18 09:00 [entrez]
AID - S0021-9258(18)30213-8 [pii]
AID - 10.1074/jbc.275.12.8982 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Mar 24;275(12):8982-90. doi: 10.1074/jbc.275.12.8982.