PKC-dependent phosphorylation may regulate the ability of connexin43 to inhibit DNA synthesis.
Phosphorylation affects several biological functions of connexin43 (Cx43), although its role on Cx43-mediated inhibition of DNA synthesis is not known. Previous studies showed increased Cx43 phosphorylation on serine in response to growth factor stimulation of cardiomyocytes, mediated by protein kinase C-epsilon (PKCepsilon). Here we report that activation of PKCepsilon is also necessary for stimulation of cardiomyocyte DNA synthesis and mitosis. We have investigated the participation of specific serine residues that are putative PKC targets in producing phosphorylated Cx43 species and also in regulating DNA synthesis in cardiomyocytes. Interference with the PKC signaling system and/or the phosphorylation of specific amino-acids of Cx43 may allow regulation of the mitogenic response.
Kardami
E
E
Institute of Cardiovascular Sciences and Departments of Anatomy and Physiology, University of Manitoba, Winnipeg, Manitoba, Canada. ekardami@sbrc.ca
Banerji
S
S
Doble
B W
BW
Dang
X
X
Fandrich
R R
RR
Jin
Y
Y
Cattini
P A
PA
D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D051381:Rats; D012694:Serine / Q000378:metabolism
D018031:Connexin 43; D016222:Fibroblast Growth Factor 2; D012694:Serine; C497257:Prkce protein, rat; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon