Association of connexin43 with a receptor protein tyrosine phosphatase.
Connexin-43(Cx43)-based gap junctional communication is transiently inhibited by certain G protein-coupled receptor agonists, including lysophosphatidic acid, endothelin and thrombin. Our previous studies have implicated the c-Src protein tyrosine kinase in mediating closure of Cx43 based gap junctions. Pervanadate, an inhibitor of protein tyrosine phosphatases, mimics activated Src in inhibiting Cx43 gap junctional communication, apparently by promoting tyrosine phosphorylation of the Cx43 C-terminal tail. However, the identity of the protein tyrosine phosphatase(s) that may normally prevent Src-induced gap junction closure is unknown. Receptor-like protein tyrosine phosphatases that mediate homotypic cell-cell interaction are attractive candidates. Here we show that receptor protein tyrosine phosphatase mu (RPTPmu) interacts with Cx43 in diverse cell systems. We find that the first catalytic domain of RPTPmu binds to Cx43. Our results support a model in which RPTPmu, or a closely related protein tyrosine phosphatase, interacts with the regulatory C-terminal tail of Cx43 to prevent Src-mediated closure of Cx43 gap junctional channels.
Giepmans
Ben N G
BN
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Feiken
Elles
E
Gebbink
Martijn F B G
MF
Moolenaar
Wouter H
WH
D000818:Animals; D019556:COS Cells; D002450:Cell Communication / Q000502:physiology*; D002522:Chlorocebus aethiops; D018031:Connexin 43 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D018031:Connexin 43; D004791:Enzyme Inhibitors; C076715:pervanadate; D014638:Vanadates; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2