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

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