PMID- 11953455
OWN - NLM
STAT- MEDLINE
DCOM- 20020419
LR  - 20221207
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 80
IP  - 6
DP  - 2002 Mar
TI  - FKHRL1 and its homologs are new targets of nerve growth factor Trk receptor 
      signaling.
PG  - 1049-61
AB  - We report that the Forkhead family of transcription factors, FKHRL1, FKHR and AFX 
      are novel components of neurotrophin receptor signaling. NGF rapidly induced the 
      phosphorylation of FKHRL1 in PC12 cells. This effect is mediated by high-affinity 
      TrkA receptor as nerve growth factor (NGF) induced the phosphorylation of FKHRL1 
      only in TrkA expressing cells and not p75-expressing cells. Additional 
      experiments with various kinase inhibitors, the transient expression of 
      constitutively active and dominant-negative Akt, and in vitro kinase assay 
      revealed that phosphatidylinositol-3 (PtdIns3)/Akt kinase mediated the actions of 
      NGF. Similar data were obtained for brain-derived neurotrophic factor (BDNF), 
      neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in primary cortical cultured 
      neurons. These findings demonstrate for the first time that the phosphorylation 
      of the Forkhead family of transcription factors can be modulated by neurotrophins 
      via Trk receptors and PtdIns3K/Akt kinase (but not MAP or S6p70 kinases) in 
      neuronal and non-neuronal cells. Moreover, survival assays with the PtdIns3 
      kinase inhibitor LY294002, active and dominant-negative forms of Akt indicate 
      that the phosphorylation of FKHRL1 plays a role in neurotrophins-mediated cell 
      survival.
FAU - Zheng, Wen-Hua
AU  - Zheng WH
AD  - Douglas Hospital Research Center, Departments of Psychiatry, and Pharmacology and 
      Therapeutics, McGill University, Montreal, Canada.
FAU - Kar, Satyabrata
AU  - Kar S
FAU - Quirion, Remi
AU  - Quirion R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (FOXO3 protein, human)
RN  - 0 (FOXO3 protein, rat)
RN  - 0 (FOXO4 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (FoxO3 protein, mouse)
RN  - 0 (Foxo1 protein, mouse)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Transcription Factors)
RN  - 0 (Foxo1 protein, rat)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - 3T3 Cells
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cell Cycle Proteins
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Forkhead Box Protein O1
MH  - Forkhead Box Protein O3
MH  - Forkhead Transcription Factors
MH  - Humans
MH  - Mice
MH  - Nerve Growth Factor/*metabolism/pharmacology
MH  - Nerve Growth Factors/pharmacology
MH  - *Nerve Tissue Proteins
MH  - Neurons/cytology/drug effects/metabolism
MH  - Neurotrophin 3/pharmacology
MH  - PC12 Cells
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation/drug effects
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Nerve Growth Factor
MH  - Receptor, trkA/antagonists & inhibitors/metabolism
MH  - Receptors, Nerve Growth Factor/metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - Transcription Factors/*metabolism
MH  - Transfection
EDAT- 2002/04/16 10:00
MHDA- 2002/04/20 10:01
CRDT- 2002/04/16 10:00
PHST- 2002/04/16 10:00 [pubmed]
PHST- 2002/04/20 10:01 [medline]
PHST- 2002/04/16 10:00 [entrez]
AID - 10.1046/j.0022-3042.2002.00783.x [doi]
PST - ppublish
SO  - J Neurochem. 2002 Mar;80(6):1049-61. doi: 10.1046/j.0022-3042.2002.00783.x.