GJA1 is so-called Connexin 43 or Cx43
Binding partners proteins of Connexin 43 (GJA1):
-Kinases: v-Src, c-Src, PKC, PKA, MAPK, Casein kinase 1, Cdc2 kinase
-TIGHT_JUNCTIONS scaffold proteins: ZO1, ZO2, caveolin 1
-Cytoskeleton: b-catenin, a-tubulin, b-tubulin
-Others: Drebrin, NOV, CIP85
Interaction between Connexin 43 (GJA1) and PKC (alpha, betat and gamma subunits)
The 3 subunits phosphorylate GJA1 at Ser368 and reduce Gap junctions activity.
Fibroblast growth factor-2 (FGF-2)decreases cardiomyocyte GJ permeability by stimulating phosphorylation of connexin-43
FGF-2 activates receptors linked to PKC and MAPK
In immunoprecipitation experiments using specific anti-Cx43 antibodies, PKCE but not PKCA coprecipitated with Cx43.
FGF-2 increased levels of coprecipitated PKCE, suggesting increased association between PKCE and Cx43 on stimulation.
To conclude, PKC mediates the FGF-2–induced effects on cardiac GJs and that PKC likely interacts with and phosphorylates cardiac Cx43 at sites of intercellular contact
Reduction of gap junctional communication in v-src transformed cells is accompanied by tyrosine phosphorylation of the gap junction protein, connexin 43
SH3 and SH2 domains of v-Src bind to proline-rich motifs and a phosphorylated tyrosine residue in the C-terminal tail of Cx43
Phosphorylation of Cx43 on S368 has been shown to decrease gap junctional communication via a reduction in unitary channel conductance.