Transduction of cell survival signals by connexin-43 hemichannels
Transduction of cell survival signals by connexin-43 hemichannels
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DOI：
10.1074/jbc.m108625200
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发表时间：
2002-03-08
影响因子：
4.8
通讯作者：
Bellido, T
中科院分区：
文献类型：
--
作者：
Plotkin, LI;Manolagas, SC;Bellido, T
双膦酸盐是一种广泛用于骨病治疗的药物，它通过细胞外信号调节激酶（ERK）激活的机制来防止成骨细胞和骨细胞凋亡。我们在此报告，六amerie连接蛋白(Cx)-43半通道，而不是间隙连接，是erk激活/抗凋亡作用的必要换能器。将Cx-43，而不是其他Cx-43转染到Cx-43初始细胞中，可获得对药物的新生反应。Cx-43的信号转导特性需要该蛋白的孔形成和c端结构域、Src和ERK激酶的激活以及Src的SH2和SH3结构域。这一证据将Cx-43添加到能够响应细胞外信号转导生存信号的跨膜蛋白列表中，并提高了它可能以这种能力为内源性分子甚至其他药物服务的可能性。
Bisphosphonates, drugs used widely in the treatment of bone diseases, prevent osteoblast and osteocyte apoptosis by a mechanism involving extracellular signal-regulated kinase (ERK) activation. We report herein that hexamerie connexin (Cx)-43 hemichannels, but not gap junctions, are the essential transducers of the ERK-activating/anti-apoptotic effects of bisphosphonates. Transfection of Cx-43, but not other Cxs, into Cx-43 naive cells confers de novo responsiveness to the drugs. The signal-transducing property of Cx-43 requires the pore forming as well as the C-terminal domains of the protein, the activation of both Src and ERK kinases, and the SH2 and SH3 domains of Src. This evidence adds Cx-43 to the list of transmembrane proteins capable of transducing survival signals in response to extracellular cues and raises the possibility that it may serve in this capacity for endogenously produced molecules or even other drugs.