Smad regulation in TGF-beta signal transduction

• Smad proteins transduce signals from transforming growth factor-beta (TGF-beta) superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. Phosphorylation of receptor-activated Smads (R-Smads) leads to formation of complexes with the common mediator Smad (Co-Smad), which are imported to the nucleus. Nuclear Smad oligomers bind to DNA and associate with transcription factors to regulate expression of target genes. Alternatively, nuclear R-Smads associate with ubiquitin ligases and promote degradation of transcriptional repressors, thus facilitating target gene regulation by TGF-beta. Smads themselves can also become ubiquitinated and are degraded by proteasomes. Finally, the inhibitory Smads (I-Smads) block phosphorylation of R-Smads by the receptors and promote ubiquitination and degradation of receptor complexes, thus inhibiting signalling.

Nyckelord

Activin Receptors; Type I/*metabolism/physiology

Animals

DNA-Binding Proteins/physiology

Humans

Phosphoproteins/physiology

Receptor Protein-Tyrosine Kinases/*metabolism/physiology

Receptors; Transforming Growth Factor beta/*metabolism/physiology

Research Support; Non-U.S. Gov't

Signal Transduction/*physiology

Trans-Activators/physiology

Transforming Growth Factor beta/*physiology

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