A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade

Mol Cell Neurosci. 1999 Jun;13(6):441-9. doi: 10.1006/mcne.1999.0758.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 Serine-Threonine Kinases / metabolism*
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / pharmacology*
  • 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

Substances

  • Adaptor Proteins, Signal Transducing
  • Enzyme Inhibitors
  • Flavonoids
  • GRB2 Adaptor Protein
  • Grb2 protein, mouse
  • Grb2 protein, rat
  • Immunoglobulin Fc Fragments
  • Peptides
  • Proteins
  • Receptors, Fibroblast Growth Factor
  • Recombinant Fusion Proteins
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • MAP Kinase Kinase 1
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases
  • Protein Tyrosine Phosphatases
  • Ptprk protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Associated data

  • GENBANK/AF142480