Signaling of transforming growth factor‐β family members through Smad proteins
Open Access
- 25 December 2000
- journal article
- review article
- Published by Wiley in European Journal of Biochemistry
- Vol. 267 (24), 6954-6967
- https://doi.org/10.1046/j.1432-1327.2000.01828.x
Abstract
Smads are pivotal intracellular nuclear effectors of transforming growth factor‐β (TGF‐β) family members. Ligand‐induced activation of TGF‐β family receptors with intrinsic serine/threonine kinase activity trigger phosphorylation of receptor‐regulated Smads (R‐Smads), whereas Smad2 and Smad3 are phosphorylated by TGF‐β, and activin type I receptors, Smad1, Smad5 and Smad8, act downstream of BMP type I receptors. Activated R‐Smads form heteromeric complexes with common‐partner Smads (Co‐Smads), e.g. Smad4, which translocate efficiently to the nucleus, where they regulate, in co‐operation with other transcription factors, coactivators and corepressors, the transcription of target genes. Inhibitory Smads act in most cases in an opposite manner from R‐ and Co‐Smads. Like other components in the TGF‐β family signaling cascade, Smad activity is intricately regulated. The multifunctional and context dependency of TGF‐β family responses are reflected in the function of Smads as signal integrators. Certain Smads are somatically mutated at high frequency in particular types of human cancers. Gene ablation of Smads in the mouse has revealed their critical roles during embryonic development. Here we review the latest advances in our understanding of the Smad mechanism of action and their in vivo functions.Keywords
This publication has 166 references indexed in Scilit:
- Interaction and Functional Cooperation of NF-κB with SmadsPublished by Elsevier BV ,2000
- A role for Smad6 in development and homeostasis of the cardiovascular systemNature Genetics, 2000
- Smad and AML Proteins Synergistically Confer Transforming Growth Factor β1 Responsiveness to Human Germ-line IgA GenesPublished by Elsevier BV ,2000
- Smad4/DPC4 Silencing and Hyperactive Ras Jointly Disrupt Transforming Growth Factor-β Antiproliferative Responses in Colon Cancer CellsPublished by Elsevier BV ,1999
- Cross-talk between the Smad1 and Ras/MEK signaling pathways for TGFβOncogene, 1999
- Role of p300, a transcriptional coactivator, in signalling of TGF‐βGenes to Cells, 1998
- Induction of Inhibitory Smad6 and Smad7 mRNA by TGF-β Family MembersBiochemical and Biophysical Research Communications, 1998
- Smad-dependent Transcriptional Activation of Human Type VII Collagen Gene (COL7A1) Promoter by Transforming Growth Factor-βPublished by Elsevier BV ,1998
- Induction of Smad6 mRNA by Bone Morphogenetic ProteinsBiochemical and Biophysical Research Communications, 1998
- Partnership between DPC4 and SMAD proteins in TGF-β signalling pathwaysNature, 1996