Hypomyelination and increased activity of voltage‐gated K + channels in mice lacking protein tyrosine phosphatase ϵ

Protein tyrosine phosphatase epsilon (PTPϵ) is strongly expressed in the nervous system; however, little is known about its physiological role. We report that mice lacking PTPϵ exhibit hypomyelination of sciatic nerve axons at an early post‐natal age. This occurs together with increased activity of delayed‐ rectifier, voltage‐gated potassium (Kv) channels and with hyperphosphorylation of Kv1.5 and Kv2.1 Kv channel α‐subunits in sciatic nerve tissue and in primary Schwann cells. PTPϵ markedly reduces Kv1.5 or Kv2.1 current amplitudes in Xenopus oocytes. Kv2.1 associates with a substrate‐trapping mutant of PTPϵ, and PTPϵ profoundly reduces Src‐ or Fyn‐stimulated Kv2.1 currents and tyrosine phosphorylation in transfected HEK 293 cells. In all, PTPϵ antagonizes activation of Kv channels by tyrosine kinases in vivo , and affects Schwann cell function during a critical period of Schwann cell growth and myelination.