Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line

被引:61
作者
Shimizu, A
Kato, M
Nakao, A
Imamura, T
ten Dijke, P
Heldin, CH
Kawabata, M
Shimada, S
Miyazono, K
机构
[1] Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Toshima Ku, Tokyo 1708455, Japan
[2] Japan Soc Promot Sci, Res Future Program, Toshima Ku, Tokyo 1708455, Japan
[3] Yamanashi Med Univ, Dept Dermatol, Yamanashi 40938, Japan
[4] Biomed Ctr, Ludwig Inst Canc Res, S-75124 Uppsala, Sweden
关键词
D O I
10.1046/j.1365-2443.1998.00174.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页码:125 / 134
页数:10
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