PMID- 17599098
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20211203
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 14
IP  - 10
DP  - 2007 Oct
TI  - Sprouty2 inhibits BDNF-induced signaling and modulates neuronal differentiation 
      and survival.
PG  - 1802-12
AB  - Sprouty (Spry) proteins are ligand-inducible inhibitors of receptor tyrosine 
      kinases-dependent signaling pathways, which control various biological processes, 
      including proliferation, differentiation and survival. Here, we investigated the 
      regulation and the role of Spry2 in cells of the central nervous system (CNS). In 
      primary cultures of immature neurons, the neurotrophic factor BDNF (brain-derived 
      neurotrophic factor) regulates spry2 expression. We identified the transcription 
      factors CREB and SP1 as important regulators of the BDNF activation of the spry2 
      promoter. In immature neurons, we show that overexpression of wild-type Spry2 
      blocks neurite formation and neurofilament light chain expression, whereas 
      inhibition of Spry2 by a dominant-negative mutant or small interfering RNA favors 
      sprouting of multiple neurites. In mature neurons that exhibit an extensive 
      neurite network, spry2 expression is sustained by BDNF and is downregulated 
      during neuronal apoptosis. Interestingly, in these differentiated neurons, 
      overexpression of Spry2 induces neuronal cell death, whereas its inhibition 
      favors neuronal survival. Together, our results imply that Spry2 is involved in 
      the development of the CNS by inhibiting both neuronal differentiation and 
      survival through a negative-feedback loop that downregulates neurotrophic 
      factors-driven signaling pathways.
FAU - Gross, I
AU  - Gross I
AD  - U682 INSERM, 3 avenue Moliere, Strasbourg 67200, France. 
      isabelle.gross@inserm.u-strasbg.fr
FAU - Armant, O
AU  - Armant O
FAU - Benosman, S
AU  - Benosman S
FAU - de Aguilar, J L G
AU  - de Aguilar JL
FAU - Freund, J-N
AU  - Freund JN
FAU - Kedinger, M
AU  - Kedinger M
FAU - Licht, J D
AU  - Licht JD
FAU - Gaiddon, C
AU  - Gaiddon C
FAU - Loeffler, J-P
AU  - Loeffler JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070629
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Sp1 Transcription Factor)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (Crebbp protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Spry2 protein, mouse)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Apoptosis
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - CREB-Binding Protein/genetics/metabolism
MH  - Cell Differentiation/*physiology
MH  - Cell Proliferation
MH  - Cell Survival/physiology
MH  - Cells, Cultured
MH  - Feedback, Physiological
MH  - Gene Expression Regulation
MH  - Intracellular Signaling Peptides and Proteins
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Neurons/*cytology/metabolism
MH  - Protein Serine-Threonine Kinases
MH  - Receptor Protein-Tyrosine Kinases/genetics/metabolism
MH  - *Signal Transduction
MH  - Sp1 Transcription Factor/genetics/metabolism
EDAT- 2007/06/30 09:00
MHDA- 2007/12/07 09:00
CRDT- 2007/06/30 09:00
PHST- 2007/06/30 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2007/06/30 09:00 [entrez]
AID - 4402188 [pii]
AID - 10.1038/sj.cdd.4402188 [doi]
PST - ppublish
SO  - Cell Death Differ. 2007 Oct;14(10):1802-12. doi: 10.1038/sj.cdd.4402188. Epub 
      2007 Jun 29.