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Smad Signal Transduction pp 177–191Cite as

Trafficking of Serine/Threonine Kinase Receptors and Smad Activation

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Part of the book series: Proteins and Cell Regulation ((PROR,volume 5))

Abstract

Signaling by the transforming growth factor-β (TGF-β) family of growth factors involves cell surface receptor serine/threonine kinases and downstream components such as SARA and Smurfs, which bind the receptor substrates called the Smad proteins. These components partition between two endocytic pathways, which lead to two separate functions in TGF-β signaling. On the one hand, clathrin-dependent endocytosis promotes signaling by leading the receptor to the early endosome where SARA is localized. On the other, non-clathrin pathways, which are enriched for the Smurf ubiquitin ligases, lead the receptor to degradation. However, in polarized cells, ligand addition induces TGF-β receptor trafficking into junctional regions of the cell where activation of Smad-dependent and -independent pathways mediates the process of epithelial-to-mesenchymal transition, which is critical during development and tumorigenesis. In this chapter, we will focus on how compartmentalization of TGF-β receptors and their downstream components controls TGF-β signaling and its biological functions

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Authors and Affiliations

  1. Center for Systems Biology, Department of Medical Genetics and Microbiology, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, M5G 1X5, Canada

    Christine Le Roy, Rohit Bose & Jeffrey L. Wrana

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  1. Christine Le Roy
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  2. Rohit Bose
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  3. Jeffrey L. Wrana
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  1. Leiden University Medical Center, Leiden, The Netherlands

    Peter ten Dijke

  2. Ludwig Institute for Cancer Research, Uppsala University, Sweden

    Carl-Henrik Heldin

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Le Roy, C., Bose, R., Wrana, J.L. (2006). Trafficking of Serine/Threonine Kinase Receptors and Smad Activation. In: Dijke, P.t., Heldin, CH. (eds) Smad Signal Transduction. Proteins and Cell Regulation, vol 5. Springer, Dordrecht. https://doi.org/10.1007/1-4020-4709-6_9

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