Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line
Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line
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DOI：
10.1046/j.1365-2443.1998.00174.x
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发表时间：
1998-02-01
期刊：
影响因子：
2.1
通讯作者：
Miyazono, K
中科院分区：
文献类型：
--
作者：
Shimizu, A;Kato, M;Miyazono, K
背景：激活素A是一种多功能蛋白，是转化生长因子- β (tgf - β)超家族的成员。Smad蛋白最近被证明可以转导tgf - β超家族蛋白的信号，而Smad2与非洲爪蟾胚胎中的激活素信号传导有关。结果：我们在人表皮角质形成细胞HaCaT中鉴定了活化素A激活的受体和Smad蛋白。HaCaT细胞上表达的激活素受体主要为激活素II型受体（activin II receptor, acr -II）和激活素IB型受体（activin IB receptor, acr -IB）。我们还表明，在HaCaT细胞中，激活素A诱导Smad3磷酸化，并在较小程度上诱导Smad2磷酸化。另一方面，tgf - β诱导Smad2和Smad3的有效磷酸化，激活素A在HaCaT细胞中优先诱导Smad3的核易位，而tgf - β强烈诱导Smad2和其他smad的核易位。此外，在转染了Smad cdna的COS细胞中，一种组成型活性的ActR-IB有效地刺激了Smad3和Smad4之间异质复合物的形成。结论：这些结果表明，激活素A与acr - ii和acr - ib受体复合物结合，并优先激活HaCaT人角质形成细胞中的Smad3。
Background: Activin A is a multifunctional protein, which is a member of the transforming growth factor-beta (TGF-beta) superfamily. Smad proteins have recently been shown to transduce signals for the TGF-beta superfamily of proteins, and Smad2 was implicated in activin signalling in Xenopus embryos.Results: We identified the receptors and Smad proteins activated by activin A in a human epidermal keratinocyte cell line, HaCaT. The major activin receptors expressed on HaCaT cells were activin type II receptor (ActR-II) and activin type IB receptor (ActR-IB). We have also shown that in HaCaT cells, activin A induced the phosphorylation of Smad3 and, to a lesser extent, of Smad2. On the other hand, TGF-beta induced an efficient phosphorylation of both Smad2 and Smad3, Activin A preferentially induced the nuclear translocation of Smad3 in HaCaT cells, whereas TGF-beta strongly induced the nuclear translocation of Smad2, as well as other Smads. Moreover, a constitutively active form of ActR-IB efficiently stimulated the formation of a heteromeric complex between Smad3 and Smad4 in COS cells transfected with Smad cDNAs.Conclusions: These results suggest that activin A binds to a receptor complex of ActR-II and ActR-IB, and preferentially activates Smad3 in HaCaT human keratinocytes.