Induction of inhibitory Smad6 and Smad7 mRNA by TGF-β family members
M Afrakhte, A Morén, S Jossan, S Itoh… - Biochemical and …, 1998 - Elsevier
M Afrakhte, A Morén, S Jossan, S Itoh, K Sampath, B Westermark, CH Heldin, NE Heldin…
Biochemical and biophysical research communications, 1998•ElsevierSmad6 and Smad7 function as intracellular antagonists in transforming growth factor-β (TGF-
β) 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-β1, activin and bone morphogenetic protein-7.
Cross-talk between TGF-β and other signaling pathways was demonstrated by the finding
that epidermal growth factor (EGF) induced the expression of inhibitory SMAD mRNA …
β) 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-β1, activin and bone morphogenetic protein-7.
Cross-talk between TGF-β and other signaling pathways was demonstrated by the finding
that epidermal growth factor (EGF) induced the expression of inhibitory SMAD mRNA …
Smad6 and Smad7 function as intracellular antagonists in transforming growth factor-β (TGF-β) 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-β1, activin and bone morphogenetic protein-7. Cross-talk between TGF-β 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-β1-induced expression of Smad7 mRNA. Ectopic expression of anti-sense Smad7 RNA was found to increase the effect of TGF-β1, supporting its role as a negative regulator in TGF-β signaling. Thus, expression of inhibitory Smads is induced by multiple stimuli, including the various TGF-β family members, whose action they antagonize.
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