Regulation of connexin43 function and expression by tyrosine kinase 2

Hanjun Li, Gaelle Spagnol, Li Zheng, Kelly L. Stauch, Paul L Sorgen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Connexin43 (Cx43) assembly and degradation, the regulation of electrical and metabolic coupling, as well as modulating the interaction with other proteins, involve phosphorylation. Here, we identified and characterized the biological significance of a novel tyrosine kinase that phosphorylates Cx43, tyrosine kinase 2 (Tyk2). Activation of Tyk2 led to a decrease in Cx43 gap junction communication by increasing the turnover rate of Cx43 from the plasma membrane. Tyk2 directly phosphorylated Cx43 residues Tyr-247 and Tyr-265, leading to indirect phosphorylation on residues Ser-279/Ser-282 (MAPK) and Ser-368 (PKC). Although this phosphorylation pattern is similar to what has been observed following Src activation, the response caused by Tyk2 occurred when Src was inactive in NRK cells. Knockdown of Tyk2 at the permissive temperature (active v-Src) in LA-25 cells decreased Cx43 phosphorylation, indicating that although activation of Tyk2 and v-Src leads to phosphorylation of the same Cx43CT residues, they are not identical in level at each site. Additionally, angiotensin II activation of Tyk2 increased the intracellular protein level of Cx43 via STAT3. These findings indicate that, like Src, Tyk2 can also inhibit gap junction communication by phosphorylating Cx43.

Original languageEnglish (US)
Pages (from-to)15867-15880
Number of pages14
JournalJournal of Biological Chemistry
Volume291
Issue number30
DOIs
StatePublished - Jul 22 2016

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TYK2 Kinase
Connexin 43
Phosphorylation
Chemical activation
Gap Junctions
src-Family Kinases
Communication
Cell membranes
Angiotensin II
Protein-Tyrosine Kinases
Proteins
Cell Membrane
Degradation
Temperature

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Regulation of connexin43 function and expression by tyrosine kinase 2. / Li, Hanjun; Spagnol, Gaelle; Zheng, Li; Stauch, Kelly L.; Sorgen, Paul L.

In: Journal of Biological Chemistry, Vol. 291, No. 30, 22.07.2016, p. 15867-15880.

Research output: Contribution to journalArticle

Li, Hanjun ; Spagnol, Gaelle ; Zheng, Li ; Stauch, Kelly L. ; Sorgen, Paul L. / Regulation of connexin43 function and expression by tyrosine kinase 2. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 30. pp. 15867-15880.
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