TAILIEUCHUNG - Báo cáo khoa học: Control of transforming growth factor b signal transduction by small GTPases

The integrated roles of small GTPases in executing the transforming growth factorb(TGFb) signaling pathway have attracted increasing atten-tion in recent years. In this review, we summarize recent findings on TGFb signaling during receptor endocytosis, Smad trafficking and actin cytoskele-ton remodeling, and emphasize the role of small GTPases in these pro-cesses. | ỊFEBS Journal REVIEW ARTICLE Control of transforming growth factor b signal transduction by small GTPases Dimitris Kardassis1 2 Carol Murphy3 Theodore Fotsis3 4 Aristidis Moustakas5 and Christos Stournaras1 1 Department of Biochemistry University of Crete Medical School Heraklion Greece 2 Institute of Molecular Biology and Biotechnology Foundation for Research Technology-Hellas Heraklion Greece 3 BiomedicalResearch Institute Foundation for Research Technology-Hellas Ioannina Greece 4 Laboratory of BiologicalChemistry University of Ioannina Medical School Greece 5 Ludwig Institute for Cancer Research Uppsala University Sweden Keywords actin cytoskeleton activin non-Smad signaling Rab Ran Ral receptor endocytosis Rho Smad signaling small GTPases TGFb trafficking Correspondence C. Stournaras Department of Biochemistry Schoolof Medicine University of Crete GR-71110 Heraklion Greece Fax 30 2810 394530 Tel 30 2810 394563 E-mail cstourn@ Received 6 February 2009 revised 11 March 2009 accepted 31 March 2009 doi The integrated roles of small GTPases in executing the transforming growth factor b TGFb signaling pathway have attracted increasing attention in recent years. In this review we summarize recent findings on TGFb 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 TGFb receptors their impact on active TGFb 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

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