TC-PTP directly interacts with connexin43 to regulate gap junction intercellular communication

Hanjun Li, Gaelle Spagnol, Naava Naslavsky, Steve Caplan, Paul L. Sorgen

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Protein kinases have long been reported to regulate connexins; however, little is known about the involvement of phosphatases in the modulation of intercellular communication through gap junctions and the subsequent downstream effects on cellular processes. Here, we identify an interaction between the T-cell protein tyrosine phosphatase (TC-PTP, officially known as PTPN2) and the carboxyl terminus of connexin43 (Cx43, officially known as GJA1). Two cell lines, normal rat kidney (NRK) cells endogenously expressing Cx43 and an NRK-derived cell line expressing v-Src with temperaturesensitive activity, were used to demonstrate that EGF and v-Src stimulation, respectively, induced TC-PTP to colocalize with Cx43 at the plasma membrane. Cell biology experiments using phosphospecific antibodies and biophysical assays demonstrated that the interaction is direct and that TC-PTP dephosphorylates Cx43 residues Y247 and Y265, but does not affect v-Src. Transfection of TC-PTP also indirectly led to the dephosphorylation of Cx43 S368, by inactivating PKCα and PKCδ, with no effect on the phosphorylation of S279 and S282 (MAPK-dependent phosphorylation sites). Dephosphorylation maintained Cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-Src-mediated phosphorylation of Cx43. Understanding dephosphorylation, along with the well-documented roles of Cx43 phosphorylation, might eventually lead to methods to modulate the regulation of gap junction channels, with potential benefits for human health.

Original languageEnglish (US)
Pages (from-to)3269-3279
Number of pages11
JournalJournal of cell science
Volume127
Issue number15
DOIs
StatePublished - 2014

Keywords

  • Connexin43
  • Gap junctions
  • Phosphorylation
  • TC-PTP
  • Tyrosine phosphatase
  • v-Src

ASJC Scopus subject areas

  • Cell Biology

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