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SMAD2 is a member of the SMAD family of proteins, intracellular proteins involved in cell signalling. Like other Smads, Smad2 plays a role in the transmission of extracellular signals from ligands of the Transforming Growth Factor beta (TGFβ) superfamily of growth factors into the cell nucleus. Binding of a subgroup of TGFβ superfamily ligands to extracellular receptors triggers phosphorylation of Smad2 at a Serine-Serine-Methionine-Serine (SSMS) motif at its extreme C-terminus. Phosphorylated Smad2 is then able to form a complex with Smad4. These complexes accumulate in the cell nucleus, where they are directly participating in the regulation of gene expression. The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants encoding the same protein have been observed.[1]
[edit] Nomenclature
The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the C. elegans protein SMA. The name is a combination of the two. During Drosophila research, it was found that a mutation in the gene, MAD, in the mother, repressed the gene, decapentaplegic, in the embryo. The phrase "Mothers against" was added since mothers often form organizations opposing various issues eg. Mothers Against Drunk Driving or (MADD). The nomenclature for this protein, like that of Sonic hedgehog, has been criticized for its frivolity.
[edit] References
[edit] Further reading
- Wrana JL (1998). "TGF-beta receptors and signalling mechanisms.". Mineral and electrolyte metabolism 24 (2-3): 120–30. PMID 9525694.
- Massagué J (1998). "TGF-beta signal transduction.". Annu. Rev. Biochem. 67: 753–91. doi:10.1146/annurev.biochem.67.1.753. PMID 9759503.
- Verschueren K, Huylebroeck D (2000). "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells.". Cytokine Growth Factor Rev. 10 (3-4): 187–99. PMID 10647776.
- Wrana JL, Attisano L (2000). "The Smad pathway.". Cytokine Growth Factor Rev. 11 (1-2): 5–13. PMID 10708948.
- Miyazono K (2000). "TGF-beta signaling by Smad proteins.". Cytokine Growth Factor Rev. 11 (1-2): 15–22. PMID 10708949.
- Zannis VI, Kan HY, Kritis A, et al. (2001). "Transcriptional regulation of the human apolipoprotein genes.". Front. Biosci. 6: D456–504. PMID 11229886.
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Cell signaling: TGF beta signaling pathway |
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| TGF beta superfamily of ligands |
TGF beta family ( TGF-β1, TGF-β2, TGF-β3)
Bone morphogenetic proteins ( BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15)
Growth differentiation factors ( GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15)
Other ( Activin A and B/ Inhibin A and B, Anti-müllerian hormone, Nodal)
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| TGF beta receptors |
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| Transducers/SMAD |
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| Ligand Inhibitors |
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| Coreceptors |
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| Other |
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