Anti-PTPRE monoclonal antibody, clone 4C22

Protein tyrosine phosphatase epsilon (PTPepsilon) is highly expressed in the nervous system; however, little is known about its physiological role. In order to study the physiological roles of the phosphatase in vivo we disrupted the single PTPe gene in mice. PTPepsilon-targeted mice 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 alpha-subunits in sciatic nerve tissue and in primary Schwann cells from Ptpre-deficient mice, In vitro studies demonstrate that catalytically active PTPepsilon markedly reduces Kv1.5 or Kv2.1 current amplitudes of Kv2.1 in Xenopus oocytes, and profoundly reduces Src- or Fyn-stimulated tyrosine phosphorylation in transfected HEK 293 cells. The interaction of these potassium channels with PTPepsilon is direct, since a substrate-trapping mutant of the phosphatase associates with Kv2.1 in transfected cells. In addition, localization of PTPC at the cell membrane is important for its ability to act on Kv channels, as p65 and p67 - two naturally occurring truncated forms of PTPe which are exclusively cytoplasmic - are significantly less active towards Kv channels compared to the membrane associated forms of the enzyme. In all, PTPepsilon antagonizes activation of Kv channels by tyrosine kinases in vivo, most likely affecting Schwann cell function during a critical period of Schwann cell growth and myelination.