Dynamic control of TGF-β signaling and its links to the cytoskeleton

Abstract 

Transforming growth factor β (TGF-β) regulates cellular behavior in embryonic and adult tissues. TGF-β binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that coordinately regulate gene expression or cytoplasmic processes such as cytoskeletal dynamics. In turn, the activity and duration of the Smad pathway seems to be regulated by cytoskeletal components, which facilitate the shuttling process that segregates Smad proteins in the cytoplasm and nucleus. We discuss mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of the TGF-β signal.

Abbreviations: ALK, activin receptor-like kinase, αSMA, α-smooth muscle actin, BMP, bone morphogenetic protein, Dpp, decapentaplegic, EMT, epithelial-mesenchymal transition, FGF, fibroblast growth factor, GDF, growth differentiation factor, GEF, guanine exchange factor, GSK3β, glycogen synthase kinase 3β, MAPK, mitogen-activated protein kinase, NES, nuclear export signal, NLS, nuclear localization signal, PI3K, phospho-inositide 3′-kinase, RTK, receptor tyrosine kinase, SBE, Smad-binding element, TAK1, TGF-β-activated kinase 1, TGF-β, transforming growth factor β

Keywords: Actin, BMP, Microtubule, Smad, Signal transduction, TGF-β, Transportin