Abstract
Receptor-like protein tyrosine phosphatase kappa (RPTPkappa) is expressed in the nervous system in a manner consistent with a role in axonal growth and guidance. The extracellular domain of RPTPkappa shares structural features with cell adhesion molecules and can support homophilic adhesion. In the present study we produced a soluble Fc-chimeric protein containing the full extracellular domain of RPTPkappa. Following affinity capture, the RPTPkappa-Fc was shown to promote the aggregation of Covasphere beads, confirming its homophilic binding activity. When added to cultures of cerebellar neurons as a soluble molecule, the RPTPkappa chimera stimulated neurite outgrowth. The neurite outgrowth response was substantially inhibited by a cell-permeable peptide inhibitor of Grb2 and by PD 098059, a drug that has been used to inhibit MEK1 activation in a wide range of cell types. These results demonstrate that RPTPkappa can stimulate neurite outgrowth and provide evidence that this might involve the coupling of Grb2 to a MAPK signal transduction cascade.
Copyright 1999 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adaptor Proteins, Signal Transducing*
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cells, Cultured
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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GRB2 Adaptor Protein
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Immunoglobulin Fc Fragments / genetics
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MAP Kinase Kinase 1
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Mice
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Mitogen-Activated Protein Kinase Kinases*
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Molecular Sequence Data
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Neurites / drug effects*
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Neurons / cytology
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Neurons / drug effects
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Peptides / pharmacology
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Protein Serine-Threonine Kinases / metabolism*
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / pharmacology*
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Protein-Tyrosine Kinases / metabolism*
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Proteins / antagonists & inhibitors
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Proteins / metabolism*
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Rats
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Receptor-Like Protein Tyrosine Phosphatases, Class 2
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Receptors, Fibroblast Growth Factor / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / pharmacology
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Signal Transduction / drug effects
Substances
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Adaptor Proteins, Signal Transducing
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Enzyme Inhibitors
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Flavonoids
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GRB2 Adaptor Protein
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Grb2 protein, mouse
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Grb2 protein, rat
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Immunoglobulin Fc Fragments
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Peptides
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Proteins
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Receptors, Fibroblast Growth Factor
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Recombinant Fusion Proteins
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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MAP Kinase Kinase 1
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Map2k1 protein, mouse
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Mitogen-Activated Protein Kinase Kinases
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Protein Tyrosine Phosphatases
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Ptprk protein, mouse
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Receptor-Like Protein Tyrosine Phosphatases, Class 2
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one