PMID- 11162678
OWN - NLM
STAT- MEDLINE
DCOM- 20010315
LR  - 20220310
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 280
IP  - 5
DP  - 2001 Feb 9
TI  - Truncated trkB.T1 is dominant negative inhibitor of trkB.TK+-mediated cell 
      survival.
PG  - 1352-8
AB  - Truncated trkB.T1 (T1) neurotrophin receptor inhibits full-length trkB.TK+ (TK+) 
      signaling. At least two possible mechanisms have been proposed for this action: 
      T1 could trap the ligand or function as a dominant negative receptor. To 
      differentiate between these possibilities we have studied survival of 
      serum-deprived PC12-trkB cells stably expressing TK+. PC12-trkB cells were 
      observed to display constitutive trkB kinase activity which leads to survival of 
      a cell subpopulation in the absence of added brain-derived neurotrophic factor 
      (BDNF) and serum. Exogenous BDNF significantly increased cell survival, and this 
      increase was inhibited by BDNF neutralizing antibody. The antibody treatment had 
      no effect on the constitutive TK+ activity. Transfected T1 completely inhibited 
      survival by BDNF or constitutive trkB kinase activity in PC12-trkB cells 
      similarly to tyrosine kinase inhibitor K252a. In addition, T1 
      coimmunoprecipitated with TK+ and inhibited its autophosphorylation by BDNF. 
      These data suggest that truncated T1 inhibits TK+ signaling by dominant negative 
      action.
FAU - Haapasalo, A
AU  - Haapasalo A
AD  - A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, 
      70211, Finland.
FAU - Koponen, E
AU  - Koponen E
FAU - Hoppe, E
AU  - Hoppe E
FAU - Wong, G
AU  - Wong G
FAU - Castren, E
AU  - Castren E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Binding Sites/genetics
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Carbazoles/pharmacology
MH  - Cell Survival/drug effects/genetics/*physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Green Fluorescent Proteins
MH  - Indole Alkaloids
MH  - Luminescent Proteins/genetics/metabolism
MH  - Mutation
MH  - PC12 Cells
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Receptor, trkB/drug effects/genetics/*metabolism
MH  - Recombinant Fusion Proteins/drug effects/genetics/metabolism
MH  - Time Factors
MH  - Transfection
EDAT- 2001/02/13 11:00
MHDA- 2001/03/17 10:01
CRDT- 2001/02/13 11:00
PHST- 2001/02/13 11:00 [pubmed]
PHST- 2001/03/17 10:01 [medline]
PHST- 2001/02/13 11:00 [entrez]
AID - S0006-291X(01)94296-2 [pii]
AID - 10.1006/bbrc.2001.4296 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2001 Feb 9;280(5):1352-8. doi: 
      10.1006/bbrc.2001.4296.