PMID- 12124436
OWN - NLM
STAT- MEDLINE
DCOM- 20020806
LR  - 20191210
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 82
IP  - 2
DP  - 2002 Jul
TI  - Shp-2 positively regulates brain-derived neurotrophic factor-promoted survival of 
      cultured ventral mesencephalic dopaminergic neurons through a brain 
      immunoglobulin-like molecule with tyrosine-based activation motifs/Shp 
      substrate-1.
PG  - 353-64
AB  - To examine the roles of Shp-2, a cytoplasmic tyrosine phosphatase, in neuronal 
      survival, we generated and used recombinant adenoviruses expressing wild type and 
      phosphatase-inactive (C/S), phosphatase domain-deficient (delta P) and 
      constitutively active (D61A and E76A) mutants of Shp-2. We found that wild-type 
      Shp-2 enhanced brain-derived neurotrophic factor (BDNF)-promoted survival of 
      cultured ventral mesencephalic dopaminergic neurons. In contrast, the C/S and 
      delta P mutants of Shp-2 did not affect survival. In addition, the constitutively 
      active D61A and E76A mutants mimicked BDNF and promoted survival. Furthermore, to 
      examine the effects of BIT/SHPS-1, a substrate of Shp-2, on the BDNF-promoted 
      survival, we generated adenovirus vectors expressing wild-type BIT/SHPS-1 and its 
      4F mutant in which all tyrosine residues in the cytoplasmic domain of BIT/SHPS-1 
      were replaced with phenylalanine. We found that BDNF-promoted survival of 
      cultured mesencephalic dopaminergic neurons was enhanced by expression of the 4F 
      mutant but not of wild-type BIT/SHPS-1. In addition, we found that co-expression 
      of wild-type BIT/SHPS-1 with Shp-2 significantly enhanced the survival-promoting 
      effect of BDNF on cultured mesencephalic dopaminergic neurons. These results 
      indicated that Shp-2 positively regulates the survival-promoting effect of BDNF 
      on cultured ventral mesencephalic dopaminergic neurons. Dephosphorylation of 
      BIT/SHPS-1 by Shp-2 may participate in BDNF-stimulated survival signaling.
FAU - Takai, Satomi
AU  - Takai S
AD  - Division of Protein Biosynthesis, Institute for Protein Research, Osaka 
      University, Suita, Japan.
FAU - Yamada, Masashi
AU  - Yamada M
FAU - Araki, Toshiyuki
AU  - Araki T
FAU - Koshimizu, Hisatsugu
AU  - Koshimizu H
FAU - Nawa, Hiroyuki
AU  - Nawa H
FAU - Hatanaka, Hiroshi
AU  - Hatanaka H
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 (Antigens, Differentiation)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neural Cell Adhesion Molecule L1)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Receptors, Immunologic)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Ptpn11 protein, rat)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - *Antigens, Differentiation
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dopamine/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Genetic Vectors/genetics/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Mesencephalon/cytology/embryology
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors
MH  - Mutagenesis, Site-Directed
MH  - *Neural Cell Adhesion Molecule L1
MH  - Neural Cell Adhesion Molecules/genetics/*metabolism
MH  - Neurons/cytology/*drug effects/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatases/genetics/*metabolism/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - *Receptors, Immunologic
EDAT- 2002/07/19 10:00
MHDA- 2002/08/07 10:01
CRDT- 2002/07/19 10:00
PHST- 2002/07/19 10:00 [pubmed]
PHST- 2002/08/07 10:01 [medline]
PHST- 2002/07/19 10:00 [entrez]
AID - 10.1046/j.1471-4159.2002.00960.x [doi]
PST - ppublish
SO  - J Neurochem. 2002 Jul;82(2):353-64. doi: 10.1046/j.1471-4159.2002.00960.x.