Selective effect of PDGF on connexin43 versus connexin40 comprised gap junction channels
Selective effect of PDGF on connexin43 versus connexin40 comprised gap junction channels
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DOI：
10.1080/714040441
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发表时间：
2003-07-01
影响因子：
--
通讯作者：
Steele, TD
中科院分区：
文献类型：
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作者：
Burt, JM;Steele, TD
本研究的目的是确定Cx40和Cx40-Cx43混合组合物接头的电导是否受血小板源性生长因子（PDGF）激活的信号级联调节，以确定赋予PDGF敏感性所需的Cx43亚基/连接子的最小数量，并确定Cx43中这种调节所需的特定残基。测定Cx40/Cx40、Cx43/Cx43、Cx40/Cx43和Cx40-Cx43/Cx40-Cx43混合组成通道的连接和通道电导（分别为g（j）和gamma（j））。PDGF对Cx40/Cx40对中的g（j）没有影响，但在其余组合中使g（j）降低53%（Cx43/Cx43）、48%（Cx40/Cx43）、41%（4：1 Cx40：Cx43表达比率）和24%（10：1 Cx40：Cx43表达比率）。基于预测的以4：1或10：1比率表达Cx40和Cx43的细胞中通道的连接蛋白组成，g（j）的这些降低表明Cx43的单个亚基足以赋予PDGF敏感性。PDGF对g（j）的作用涉及γ（j）和Po的降低，并且需要C-末端的丝氨酸368。这些数据暗示蛋白激酶C作为PDGF效应的介体，并强烈表明PDGF激活的信号级联对间隙连接功能的急性调节是由细胞中敏感连接蛋白的低水平表达赋予的，否则表达不敏感连接蛋白。
The goals of the current study were to determine whether the conductance of Cx40 and Cx40-Cx43 mixed composition junctions was regulated by platelet-derived growth factor (PDGF)-activated signaling cascades, to ascertain the minimum number of Cx43 subunits/connexon required to confer PDGF sensitivity, and to identify specific residues in Cx43 required for this regulation. Junctional and channel conductances (g(j) and gamma(j) , respectively) were determined for Cx40/Cx40, Cx43/Cx43, Cx40/Cx43, and Cx40-Cx43/Cx40-Cx43 mixed composition channels. PDGF had no effect on g(j) in Cx40/Cx40 pairs, but decreased g(j) in the remaining combinations by 53% (Cx43/Cx43), 48% (Cx40/Cx43), 41% (4:1 Cx40:Cx43 expression ratio) and 24% (10:1 Cx40:Cx43 expression ratio). Based on the predicted connexin composition of channels in cells expressing Cx40 and Cx43 at either 4:1 or 10:1 ratios, these decreases in g(j) suggest that a single subunit of Cx43 is sufficient to confer PDGF sensitivity. The effect of PDGF on g(j) involved a decrease in both gamma(j) and Po and required serine 368 in the C-terminus. These data implicate protein kinase C as the mediator of the PDGF effect and strongly suggest that acute regulation of gap junction function by PDGF-activated signaling cascades is conferred by low levels of expression of a sensitive connexin in cells that otherwise express insensitive connexins.