SIGN IN   Advanced Search

Browse Illustration
Crossing Smads

The transforming growth factor–β (TGF-β) superfamily is a group of polypeptide growth factors that are secreted from cells as dimeric molecules. Members of this family regulate early development, organogenesis, and homeostasis, and mutations of this pathway are associated with human diseases (including cancer) and with hereditary conditions such as persistent Mullerian duct syndrome, Hunter-Thompson acromesomelic chondrodysplasia, and hereditary hemorrhagic telangiectasia. The TGF-β family regulates cellular function by activating a unique family of transmembrane serine-threonine kinase receptors. These receptors then translate binding of the TGF-β ligand into an intracellular signal. This is achieved by the activation of a family of intracellular signal transduction molecules known as Smads. When activated by the receptor, different types of Smads assemble into heteromeric complexes and translocate into the nucleus, where they interact with a host of DNA binding proteins to regulate transcription. Thus, Smads transmit TGF-β signals directly from the cell surface receptor to nuclear transcription factors. In the nucleus, one class of Smad partners, exemplified by the DNA binding protein FAST, cannot regulate transcription in the absence of Smad protein. However, when Smads bind to FAST protein, they cause activation of genes that contain FAST binding sites in their promoters. In these cases, Smads represent a primary regulatory signal. In contrast, members of the second group of Smad partners control transcription in the absence of Smads and can be regulated by other signaling pathways. In these cases, Smads represent a secondary signal that augments transcription (or, in some examples, represses transcription) mediated by these partners. Smads can be thought of as transcriptional comodulators that modify the output of these other signaling pathways. This "crosstalk" in the nucleus allows Smads to control a diverse array of transcriptional outputs in response to TGF-β stimulation of cells.

Rate this Resource:
1 = not useful, 5 = very useful

Please be the first to rate this resource.

Subscribe and
View Resource


Resource Type: Bibliography, Diagram, Illustration, Journal article/Issue, Review
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright

Authors and Editors: Jeffrey L. Wrana of Mount Sinai Hospital and Department of Medical Genetics and Microbiology, University of Toronto
Publisher: American Association for the Advancement of Science
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes


» Sign In or register to post comments.

STKE/Science Signaling



Triple A S National Science Foundation Naitonal Science Digital Library Pathway
Funded by the individual BEN Collaborators and grants from the
National Science Foundation [DUE 0085840 / DUE 0226185 / DUE 0532797 / DUE 0734995]

This website is a National Science Digital Library (NSDL) Pathway.
Copyright © 2019. American Association for the Advancement of Science. All Rights Reserved.