Identifiers
gap junction protein, alpha 1, 43kDa
HUGO:GJA1, HGNC:4274, ENTREZ:2697, UNIPROT:P17302, GENECARDS:GC06P121756 ??
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / CELL_CELL_ADHESIONS
EMT Senescence / GAP_JUNCTIONS
References
PMID:16359940
PMID:14576341
Among the Connexins, Cx43 (GJA1) is the most ubiquitously expressed.
Cx43 is endogenously expressed in at least 35 distinct tissues encompassing over 35 cell types that include cardiomyocytes, keratinocytes, astrocytes, endothelial cells and smooth-muscle cells among many others.
Cx43 co-oligomerize with other Connexins like Cx26 (GJB2, keratinocytes and hepatocytes), Cx31 (GJB5, keratinocytes), Cx45 (GJC1, myocardium) and Cx46 (GJA3, trans-Golgi network).
However Cx43 is unable to co-oligomerize with Cx32 (GJB1).
PMID:16492141
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
Cx43 binds with ZO-1 and ZO-2, at different stages of the cell cycle to regulate Gap Junctions size and stability;
Cx43 interacts directly with b-Catenin to regulate Gap junctional intercelullar communication cross-talk activity with the WNT signaling (essential for cell survival);
Binding of CIP85 to Cx43 regulates the turnover of Cx43-containing Gap Junctions, stabilizing the junctions.
Drebrin 1 (Actin-binding protein) binds Cx43 and links Gap junctions to the sub-membrane cytoskeleton
Other cytoskeletal proteins like a and b-Tubulin bind with Cx43 to facilitate Connexion transport.
Binding of NOV to the C-terminus of Cx43 potentially regulates growth suppression.
Binding of Cx43 to Caveolin-1 may play a role in internalization of Cx43.
Connexin-specific selectivity:
Homomeric Connexons made up of Cx32 are permeable both to cAMP and cGMP
Heteromeric Connexons containing both Cx26 (GJB2) and Cx32 are not permeable to cAMP but allow passage of cGMP
References
em_emtc_emtc_re481( EMT Senescence ):
GJA1 is so-called Connexin 43 or Cx43
PMID:16492141
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
PMID:10871288
Interaction between Connexin 43 (GJA1) and PKC (alpha, betat and gamma subunits)
The 3 subunits phosphorylate GJA1 at Ser368 and reduce Gap junctions activity.
PMID:10679481
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
PMID:9278444
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
PMID:15534005
Phosphorylation of Cx43 on S368 has been shown to decrease gap junctional communication via a reduction in unitary channel conductance.
em_emtc_emtc_re538( EMT Senescence ):
PMID:15980428
PMID:19284610
The associations between Cx43 and ZO-1 and ZO-2 proteins were shown to be under cell-cycle stage-specific control.
Connexin 43 interacts preferentially
with ZO-1 during G0 stage, whereas the interaction with ZO-2 is approximately the same during the various stages
em_emtc_emtc_re649( EMT Senescence ):
PMID:22022608
Connexin43 modulates cell polarity and directional cell migration by regulating microtubule dynamics.
References
em_emtc_emtc_re481( EMT Senescence ):
GJA1 is so-called Connexin 43 or Cx43
PMID:16492141
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
PMID:10871288
Interaction between Connexin 43 (GJA1) and PKC (alpha, betat and gamma subunits)
The 3 subunits phosphorylate GJA1 at Ser368 and reduce Gap junctions activity.
PMID:10679481
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
PMID:9278444
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
PMID:15534005
Phosphorylation of Cx43 on S368 has been shown to decrease gap junctional communication via a reduction in unitary channel conductance.
+ ATP@Cytosol → GJA1|pho@Cytosol + ADP@Cytosol
+ GJA1@Cytosol → GJA1:GJA1_4_GJC1*@Neighbouring Cell
+ ZO1*@Cytosol → GJA1:ZO1*@Cytosol
→ GJA1@Neighbouring Cell
→ GJA1@Neighbouring Cell
→ GJA1@Neighbouring Cell
→ Gap junctions@Cytosol
→ Migratory polarity@Nucleus
→ Cell motility@Cytosol
→ Tight junctions@Neighbouring Cell
+ GJA1@Cytosol → GJA1:ZO2*@Cytosol
→ G0 phase@Cytosol
→ Proliferation@Cytosol