A Soluble Version of the Receptor-like Protein Tyrosine Phosphatase κ Stimulates Neurite Outgrowth via a Grb2/MEK1-Dependent Signaling Cascade

• Published in: Molecular and cellular neuroscience 1999-06, Vol.13 (6), p.441-449
• Main Authors: Drosopoulos, Natalia E., Walsh, Frank S., Doherty, Patrick
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Adaptor Proteins, Signal Transducing; Animals; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; GRB2 Adaptor Protein; Immunoglobulin Fc Fragments - genetics; MAP Kinase Kinase 1; Mice; Mitogen-Activated Protein Kinase Kinases; Molecular Sequence Data; Neurites - drug effects; Neurons - cytology; Neurons - drug effects; Peptides - pharmacology; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - pharmacology; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - metabolism; Proteins - antagonists & inhibitors; Proteins - metabolism; Rats; Receptor-Like Protein Tyrosine Phosphatases, Class 2; Receptors, Fibroblast Growth Factor - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - pharmacology; Signal Transduction - drug effects
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1006/mcne.1999.0758

Receptor-like protein tyrosine phosphatase κ (RPTPκ) is expressed in the nervous system in a manner consistent with a role in axonal growth and guidance. The extracellular domain of RPTPκ 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 RPTPκ. Following affinity capture, the RPTPκ–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 RPTPκ 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 RPTPκ can stimulate neurite outgrowth and provide evidence that this might involve the coupling of Grb2 to a MAPK signal transduction cascade.