Tyrosine phosphorylation of the gap junction protein connexin43 is required for the pp60v-src-induced inhibition of communication

Cell Regul. 1990 Dec;1(13):989-1002. doi: 10.1091/mbc.1.13.989.


Gap junction communication in some cells has been shown to be inhibited by pp60v-src, a protein tyrosine kinase encoded by the viral oncogene v-src. The gap junction protein connexin43 (Cx43) has been shown to be phosphorylated on serine in the absence of pp60v-src and on both serine and tyrosine in cells expressing pp60v-src. However, it is not known if the effect of v-src expression on communication results directly from tyrosine phosphorylation of the Cx43 or indirectly, for example, by activation of other second-messenger systems. In addition, the effect of v-src expression on communication based on other connexins has not been examined. We have used a functional expression system consisting of paired Xenopus oocytes to examine the effect of v-src expression on the regulation of communication by gap junctions comprised of different connexins. Expression of pp60v-src completely blocked the communication induced by Cx43 but had only a modest effect on communication induced by connexin32 (Cx32). Phosphoamino acid analysis showed that pp60v-src induced tyrosine phosphorylation of Cx43, but not Cx32. A mutation replacing tyrosine 265 of Cx43 with phenylalanine abolished both the inhibition of communication and the tyrosine phosphorylation induced by pp60v-src without affecting the ability of this protein to form gap junctions. These data show that the effect of pp60v-src on gap junctional communication is connexin specific and that the inhibition of Cx43-mediated junctional communication by pp60v-src requires tyrosine phosphorylation of Cx43.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Communication / physiology*
  • Cell Division / physiology
  • Connexins
  • Gene Expression / physiology
  • Membrane Proteins / metabolism*
  • Microinjections
  • Molecular Sequence Data
  • Oncogene Protein pp60(v-src) / metabolism*
  • Oocytes / metabolism*
  • Phosphorylation
  • RNA, Messenger / metabolism
  • Serine / metabolism
  • Tyrosine / metabolism*
  • Xenopus


  • Connexins
  • Membrane Proteins
  • RNA, Messenger
  • Tyrosine
  • Serine
  • Oncogene Protein pp60(v-src)