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TGF-β signalling from cell membrane to nucleus through SMAD proteins

Abstract

The recent identification of the SMAD family of signal transducer proteins has unravelled the mechanisms by which transforming growth factor-β (TGF-β) signals from the cell membrane to the nucleus. Pathway-restricted SMADs are phosphorylated by specific cell-surface receptors that have serine/threonine kinase activity, then they oligomerize with the common mediator Smad4 and translocate to the nucleus where they direct transcription to effect the cell's response to TGF-β. Inhibitory SMADs have been identified that block the activation of these pathway-restricted SMADs.

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Figure 1: An activated TGF-β-receptor complex.
Figure 2: The SMAD family.
Figure 3: Agonistic and antagonistic SMAD proteins in TGF-β signalling.
Figure 4: Different functional domains in SMADs.

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We thank I. Schiller for help in the preparation of this manuscript. We apologize to all those authors whose work we have been unable to cite because of space constraints.

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Heldin, CH., Miyazono, K. & ten Dijke, P. TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature 390, 465–471 (1997). https://doi.org/10.1038/37284

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