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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-7-18
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation, http://linkedlifedata.com/resource/pubmed/chemical/Brain-Derived Neurotrophic Factor, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Neural Cell Adhesion Molecule L1, http://linkedlifedata.com/resource/pubmed/chemical/Neural Cell Adhesion Molecules, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase..., http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
353-64
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12124436-Animals, pubmed-meshheading:12124436-Antigens, Differentiation, pubmed-meshheading:12124436-Brain-Derived Neurotrophic Factor, pubmed-meshheading:12124436-Cell Survival, pubmed-meshheading:12124436-Cells, Cultured, pubmed-meshheading:12124436-Dopamine, pubmed-meshheading:12124436-Enzyme Inhibitors, pubmed-meshheading:12124436-Female, pubmed-meshheading:12124436-Genetic Vectors, pubmed-meshheading:12124436-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:12124436-Male, pubmed-meshheading:12124436-Membrane Glycoproteins, pubmed-meshheading:12124436-Mesencephalon, pubmed-meshheading:12124436-Mitogen-Activated Protein Kinases, pubmed-meshheading:12124436-Mutagenesis, Site-Directed, pubmed-meshheading:12124436-Neural Cell Adhesion Molecule L1, pubmed-meshheading:12124436-Neural Cell Adhesion Molecules, pubmed-meshheading:12124436-Neurons, pubmed-meshheading:12124436-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12124436-Phosphorylation, pubmed-meshheading:12124436-Protein Tyrosine Phosphatase, Non-Receptor Type 11, pubmed-meshheading:12124436-Protein Tyrosine Phosphatases, pubmed-meshheading:12124436-Rats, pubmed-meshheading:12124436-Rats, Wistar, pubmed-meshheading:12124436-Receptors, Immunologic
pubmed:year
2002
pubmed:articleTitle
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.
pubmed:affiliation
Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Suita, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't