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Can't get no SMADisfaction: Smad proteins as positive and negative regulators of TGF-β family signals

✍ Scribed by Jan L. Christian; Takuya Nakayama


Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
475 KB
Volume
21
Category
Article
ISSN
0265-9247

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✦ Synopsis


The identification of Smad proteins as molecular components of the transforming growth factor-␤ (TGF-␤) signaling cascade has enhanced our understanding of how ligand-mediated activation of TGF-␤ receptors leads to modulation of target gene transcription. Recent studies have identified a distinct, structurally related class of Smads which inhibits, rather than transduces, TGF-␤ family signals. The molecular mechanism of action and the exact signaling pathways that are targeted by antagonistic Smads are not completely understood. These proteins appear to participate in autoregulatory negative feedback loops in which signaling initiated by specific TGF-␤ family ligands induces the expression of an inhibitory Smad that then functions to modulate the amplitude or duration of signaling. Negative feedback circuits such as these play important roles in fine-tuning the activity of multifunctional signaling molecules during embryonic patterning and in response to pathologic stimuli in adults.