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Cited by 256

The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.

Cellular interpretation of multiple TGF-β signals: intracellular antagonism between activin/BVg1 and BMP-2/4 signaling mediated by Smads

Candia, Albert F., Watabe, Tetsuro, Hawley, Stephanie H. B., Onichtchouk, Darya, Zhang, Ying, Derynck, Rik, Niehrs, Christof, Cho, Ken W. Y.·1997·Development
DOI 10.1242/dev.124.22.4467
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Abstract

During early embryogenesis of Xenopus, dorsoventral polarity of the mesoderm is established by dorsalizing and ventralizing agents, which are presumably mediated by the activity of an activin/BVg1-like protein and Bone Morphogenetic Proteins (BMP), respectively. Interestingly, these two TGF-β subfamilies are found in overlapping regions during mesoderm patterning. This raises the question of how the presumptive mesodermal cells recognize the multiple TGF-β signals and differentially interpret this information to assign a particular cell fate. In this study, we have exploited the well characterized model of Xenopus mesoderm induction to determine the intracellular interactions between BMP-2/4 and activin/BVg1 signaling cascades. Using a constitutively active BMP-2/4 receptor that transduces BMP-2/4 signals in a ligand-independent fashion, we demonstrate that signals provided by activin/BVg1 and BMP modulate each other’s activity and that this crosstalk occurs through intracellular mechanisms. In assays using BMP-2/4 and activin/BVg1-specific reporters, we determined that the specificity of BMP-2/4 and activin/BVg1 signaling is mediated by Smad1 and Smad2, respectively. These Smads should be considered as the mediators of the intracellular antagonism between BMP-2/4 and activin/BVg1 signaling possibly through sequestration of a limited pool of Smad4. Consistent with such a mechanism, Smad4 interacts functionally with both Smad1 and −2 to potentiate their signaling activities, and a dominant negative variant of Smad4 can inhibit both activin/BVg1 and BMP-2/4 mediated signaling Finally, we demonstrate that an activin/BVg1-dependent transcriptional complex contains both Smad2 and Smad4 and thereby provides a physical basis for the functional involvement of both Smads in TGF-β-dependent transcriptional regulation. Thus, Smad4 plays a central role in synergistically activating activin/BVg1 and BMP-dependent transcription and functions as an intracellular sensor for TGFβ-related signals.

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Metadata

Authors
Candia, A. F., Watabe, T., Hawley, S. H. B., Onichtchouk, D., Zhang, Y., Derynck, R., Niehrs, C., & Cho, K. W. Y.
Venue
Development
Publisher
The Company of Biologists
Published
1997-11-15
Volume
124
Issue
22
Pages
4467-4480
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.124.22.4467
OpenAlex
W2296436253
Cited by
256
References
61
FWCI
7.99
Type
journal article
Language
en
Open access
closed

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