PKC-Dependent Phosphorylation May Regulate the Ability of Connexin43 to Inhibit DNA Synthesis

E. Kardami Institute of Cardiovascular Sciences and Departments of Anatomy and Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

S. Banerji Institute of Cardiovascular Sciences and Departments of Anatomy and Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

B. W. Doble Institute of Cardiovascular Sciences and Departments of Anatomy and Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

X. Dang Institute of Cardiovascular Sciences and Departments of Anatomy and Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

R. R. Fandrich Institute of Cardiovascular Sciences and Departments of Anatomy and Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

Y. Jin Institute of Cardiovascular Sciences and Departments of Anatomy and Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

P. A. Cattini Institute of Cardiovascular Sciences and Departments of Anatomy and Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

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Abstract

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 (PKCε). Here we report that activation of PKCε 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.

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PKC-Dependent Phosphorylation May Regulate the Ability of Connexin43 to Inhibit DNA Synthesis

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PKC-Dependent Phosphorylation May Regulate the Ability of Connexin43 to Inhibit DNA Synthesis

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