Regulation of Smad activities

TGF-beta (Transforming Growth Factor-beta) cytokines employ Smad proteins as the intracellular mediator of signaling. Upon TGF-beta stimulation, the cytoplasmic Smads become phosphorylated and consequently accumulate in the nucleus to regulate target gene expression. The cytoplasm-to-nucleus redistribution of Smads, as well as the ability of Smads to activate or repress gene transcription, is under multiple layers of regulation by factors not limited to TGF-beta. With recent advance in the knowledge of regulatory factors impinged oil Smads, we are beginning to understand the coiriplexity in cellular responses to TGF-beta. (c) 2006 Elsevier B.V. All rights reserved.