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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收藏
页码:125 / 134
页数:10
相关论文
共 58 条
[51]   ACTIVIN/INHIBIN BETA-B SUBUNIT GENE DISRUPTION LEADS TO DEFECTS IN EYELID DEVELOPMENT AND FEMALE REPRODUCTION [J].
VASSALLI, A ;
MATZUK, MM ;
GARDNER, HAR ;
LEE, KF ;
JAENISCH, R .
GENES & DEVELOPMENT, 1994, 8 (04) :414-427
[52]  
Wataya-Kaneda Mari, 1994, Journal of Dermatological Science, V8, P38, DOI 10.1016/0923-1811(94)90319-0
[53]   Formation and activation by phosphorylation of activin receptor complexes [J].
Willis, SA ;
Zimmerman, CM ;
Li, L ;
Mathews, LS .
MOLECULAR ENDOCRINOLOGY, 1996, 10 (04) :367-379
[54]   Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4 [J].
Wu, RY ;
Zhang, Y ;
Feng, XH ;
Derynck, R .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (05) :2521-2528
[55]   IDENTIFICATION OF A MEMBER OF THE MAPKKK FAMILY AS A POTENTIAL MEDIATOR OF TGF-BETA SIGNAL-TRANSDUCTION [J].
YAMAGUCHI, K ;
SHIRAKABE, T ;
SHIBUYA, H ;
IRIE, K ;
OISHI, I ;
UENO, N ;
TANIGUCHI, T ;
NISHIDA, E ;
MATSUMOTO, K .
SCIENCE, 1995, 270 (5244) :2008-2011
[56]   ACTIVIN-A - AN AUTOCRINE INHIBITOR OF INITIATION OF DNA-SYNTHESIS IN RAT HEPATOCYTES [J].
YASUDA, H ;
MINE, T ;
SHIBATA, H ;
ETO, Y ;
HASEGAWA, Y ;
TAKEUCHI, T ;
ASANO, S ;
KOJIMA, I .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (03) :1491-1496
[57]   The tumor suppressor Smad4 DPC 4 as a central mediator of Smad function [J].
Zhang, Y ;
Musci, T ;
Derynck, R .
CURRENT BIOLOGY, 1997, 7 (04) :270-276
[58]   Receptor-associated Mad homologues synergize as effectors of the TGF-beta response [J].
Zhang, Y ;
Feng, XH ;
Wu, RY ;
Derynck, R .
NATURE, 1996, 383 (6596) :168-172