Regulation of connexin-43-mediated growth inhibition by a phosphorylatable amino-acid is independent of gap junction-forming ability

被引:40
作者
Dang, Xitong
Jeyaraman, Madhumathy
Kardami, Elissavet
机构
[1] St Boniface Res Ctr, Inst Cardiovasc Sci, Winnipeg, MB R2H 2A6, Canada
[2] Univ Manitoba, Dept Human Anat, Winnipeg, MB R2H 2A6, Canada
[3] Univ Manitoba, Dept Cell Sci & Physiol, Winnipeg, MB R2H 2A6, Canada
基金
加拿大健康研究院;
关键词
growth regulation; connexins; phosphorylation; structure-function; protein kinase C;
D O I
10.1007/s11010-006-9162-2
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The ability of the gap junction phosphoprotein connexin-43 (Cx43) to inhibit DNA synthesis in primary cardiomyocytes is regulated by serine (S) 262, a protein kinase C phosphorylation site that also affects metabolic coupling. We have now examined if the S262-regulated growth suppression is operating in transformed cells and if so whether it depends on gap junction channel forming ability. Serine 262 became phosphorylated in response to protein kinase C stimulation in HEK293 cells transiently expressing either Cx43 or the non-channel-forming carboxy-terminal tail of Cx43 (Cx43CT). Expression of either wild type Cx43 or Cx43CT inhibited DNA synthesis, as did their mutated versions simulating lack of phosphorylation by carrying an S262-to-alanine substitution. The ability to inhibit DNA synthesis was eliminated when expressing mutated versions of either Cx43 or Cx43CT simulating constitutive phosphorylation by carrying an S262-to-aspartate substitution. We conclude that S262 phosphorylation cancels growth inhibition by Cx43 independently of channel-forming ability.
引用
收藏
页码:201 / 207
页数:7
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