Induction of inhibitory Smad6 and Smad7 mRNA by TGF-β family members

被引:296
|
作者
Afrakhte, M [1 ]
Morén, A
Jossan, S
Itoh, S
Westermark, B
Heldin, CH
Heldin, NE
ten Dijke, P
机构
[1] Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
[2] Ludwig Inst Canc Res, Ctr Biomed, S-75124 Uppsala, Sweden
[3] Creat Biomol Inc, Hopkinton, MA 01748 USA
关键词
D O I
10.1006/bbrc.1998.9170
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Smad6 and Smad7 function as intracellular antagonists in transforming growth factor-beta (TGF-beta) signaling. Here we report the isolation of human Smad6, which is closely related to Smad7. Smad6 and Smad7 mRNAs were differentially expressed in lung cancer cell lines and were rapidly and directly induced by TGF-beta 1, activin and bone morphogenetic protein-7. Cross-talk between TGF-beta and other signaling pathways was demonstrated by the finding that epidermal growth factor (EGF) induced the expression of inhibitory SMAD mRNA. Moreover, whereas the phorbol ester PMA. alone had no effect, it potentiated the TGF-beta 1-induced expression of Smad7 mRNA. Ectopic expression of anti-sense Smad7 RNA was found to increase the effect of TGF-beta 1, supporting its role as a negative regulator in TGF-beta signaling. Thus, expression of inhibitory Smads is induced by multiple stimuli, including the various TGF-beta family members, whose action they antagonize. (C) 1998 Academic Press.
引用
收藏
页码:505 / 511
页数:7
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