title: A sodium channel signaling complex: modulation by associated receptor protein tyrosine phosphatase beta.
abstract: Voltage-gated sodium channels in brain neurons were found to associate with receptor protein tyrosine phosphatase beta (RPTPbeta) and its catalytically inactive, secreted isoform phosphacan, and this interaction was regulated during development. Both the extracellular domain and the intracellular catalytic domain of RPTPbeta interacted with sodium channels. Sodium channels were tyrosine phosphorylated and were modulated by the associated catalytic domains of RPTPbeta. Dephosphorylation slowed sodium channel inactivation, positively shifted its voltage dependence, and increased whole-cell sodium current. Our results define a sodium channel signaling complex containing RPTPbeta, which acts to regulate sodium channel modulation by tyrosine phosphorylation.
authors.affiliation: Department of Pharmacology, Mailstop 357280, University of Washington, Seattle, Washington 98195-7280, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Ratcliffe
authors.forename: Y
authors.initials: Y
authors.lastname: Qu
authors.forename: K A
authors.initials: KA
authors.lastname: McCormick
authors.forename: V C
authors.initials: VC
authors.lastname: Tibbs
authors.forename: J E
authors.initials: JE
authors.lastname: Dixon
authors.forename: T
authors.initials: T
authors.lastname: Scheuer
authors.forename: W A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000166:cytology; D002256:Carbonic Anhydrases / Q000737:chemistry; D020134:Catalytic Domain; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D015222:Sodium Channels; D019000:Phosphotyrosine; D012964:Sodium; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D002256:Carbonic Anhydrases