Connexin43 recruits PTEN and Csk to inhibit c-Src activity in glioma cells and astrocytes

摘要: // Ana Gonzalez-Sanchez 1 , Myriam Jaraiz-Rodriguez Marta Dominguez-Prieto Sandra Herrero-Gonzalez Jose M. Medina Arantxa Tabernero Instituto de Neurociencias Castilla y Leon (INCYL), Departamento Bioquimica Biologia Molecular, Universidad Salamanca, Spain Correspondence to: Tabernero, email: ataber@usal.es Keywords: connexin, Src, glia, CNS, gap junctions Received: December 10, 2015      Accepted: June 26, 2016      Published: July 06, 2016 ABSTRACT Connexin43 (Cx43), the major protein forming in astrocytes, is reduced high-grade gliomas, where its ectopic expression exerts important effects, including inhibition of proto-oncogene tyrosine-protein kinase Src (c-Src). In this work we aimed to investigate mechanism responsible for effect. The c-Src requires phosphorylation at tyrosine 527 mediated by C-terminal (Csk) and dephosphorylation 416 phosphatases, such as phosphatase tensin homolog (PTEN). Our results showed that antiproliferative effect Cx43 when Csk PTEN are silenced glioma cells, suggesting involvement both enzymes. Confocal microscopy immunoprecipitation assays confirmed Cx43, addition c-Src, binds cells transfected with astrocytes. Pull-down region 266–283 sufficient recruit inhibit oncogenic activity c-Src. As a result inhibition, was increased subsequent inactivation Akt reduction proliferation human glioblastoma stem cells. We conclude recruitment between residues 266 283 within C-terminus leads inhibition.