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Control of transforming growth factor beta signal transduction by small GTPases
Department of Biochemistry, University of Crete Medical School, Heraklion, Greece.
Biomedical Research Institute, Foundation for Research & Technology-Hellas, Ioannina, Greece.
Biomedical Research Institute, Foundation for Research & Technology-Hellas, Ioannina, Greece.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
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2009 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 11, 2947-2965 p.Article, review/survey (Refereed) Published
Abstract [en]

The integrated roles of small GTPases in executing the transforming growth factor beta (TGFbeta) signaling pathway have attracted increasing attention in recent years. In this review, we summarize recent findings on TGFbeta signaling during receptor endocytosis, Smad trafficking and actin cytoskeleton remodeling, and emphasize the role of small GTPases in these processes. First, we give an overview of the different endocytic routes taken by TGFbeta receptors, their impact on active TGFbeta signaling versus degradation and their regulation by the small GTPases Rab, RalA/Ral-binding protein 1 and Rap2. Second, we focus on the mechanisms and regulation of Smad trafficking in the cytoplasm, through the nuclear pores and into the nucleus, and the contribution of Ran GTPase to these events. Third, we summarize the role of Rho small GTPases in early and late cytoskeleton remodeling in various cell models and diseases, and the positive and negative cross-talk between Rho GTPases and the TGFbeta/Smad pathway. The biological significance of this exciting research field, the perspectives and critical open questions are discussed.

Place, publisher, year, edition, pages
2009. Vol. 276, no 11, 2947-2965 p.
Keyword [en]
Actin cytoskeleton, activin, non-Smad signaling, Rab ⁄ Ran ⁄ Ral, receptor endocytosis, Rho, Smad signaling, small GTPases, TGFb, trafficking
National Category
Natural Sciences Medical and Health Sciences
URN: urn:nbn:se:uu:diva-105791DOI: 10.1111/j.1742-4658.2009.07031.xISI: 000265934500006PubMedID: 19490100OAI: oai:DiVA.org:uu-105791DiVA: diva2:222449
Available from: 2009-06-08 Created: 2009-06-08 Last updated: 2011-01-18Bibliographically approved

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