SMAD (protein)

SMADs are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus where they activate downstream gene transcription.^{[1][2][3][4][5][6]}

The SMADs, which form a trimer of two receptor-regulated SMADs and one co-SMAD, act as transcription factors that regulate the expression of certain genes.^[7][8]

Classes

There are three classes of SMAD:

1. The receptor-regulated Smads (R-SMAD) which include SMAD1, SMAD2, SMAD3, SMAD5 and SMAD8/9^[9]
2. The common-mediator Smad (co-SMAD) which includes only SMAD4, which interacts with R-SMADs to participate in signaling^[10]
3. The antagonistic or inhibitory Smads (I-SMAD) which include SMAD6 and SMAD7, which block the activation of R-SMADs and Co-SMADs.^[11]

Nomenclature

The SMAD proteins are homologs of both the Drosophila protein, mothers against decapentaplegic (MAD^[12]) and the Caenorhabditis elegans protein SMA (from gene sma for small body size^[13]). The name is a portmanteau of the two. MAD mutations can be placed in an allelic series based on the relative severity of the maternal effect enhancement of weak dpp alleles, thus explaining the name Mothers against dpp.^[14]

During Drosophila research, it was found that a mutation in the gene, MAD, in the mother, repressed the gene decapentaplegic in the embryo.

Hair

Specifically, colocalization of phosphorylated Smad1/5/8 complex and DLX3 regulate role for BMP signaling to Dlx3 during hair morphogenesis in animal models.^[15][16]

References

1. Heldin CH, Miyazono K, ten Dijke P (December 1997). "TGF-beta signalling from cell membrane to nucleus through SMAD proteins". Nature 390 (6659): 465–71. doi:10.1038/37284. PMID 9393997.
2. Attisano L, Wrana JL (April 1998). "Mads and Smads in TGF beta signalling". Curr. Opin. Cell Biol. 10 (2): 188–94. doi:10.1016/S0955-0674(98)80141-5. PMID 9561843.
3. Massagué J (1998). "TGF-beta signal transduction". Annu. Rev. Biochem. 67: 753–91. doi:10.1146/annurev.biochem.67.1.753. PMID 9759503.
4. Attisano L, Wrana JL (May 2002). "Signal transduction by the TGF-beta superfamily". Science 296 (5573): 1646–7. doi:10.1126/science.1071809. PMID 12040180.
5. Whitman M (August 1998). "Smads and early developmental signaling by the TGFbeta superfamily". Genes Dev. 12 (16): 2445–62. doi:10.1101/gad.12.16.2445. PMID 9716398.
6. Wrana JL (March 2000). "Crossing Smads". Sci. STKE 2000 (23): RE1. doi:10.1126/stke.2000.23.re1. PMID 11752591.
7. Derynck R, Zhang Y, Feng XH (December 1998). "Smads: transcriptional activators of TGF-beta responses". Cell 95 (6): 737–40. doi:10.1016/S0092-8674(00)81696-7. PMID 9865691.
8. Massagué J, Seoane J, Wotton D (December 2005). "Smad transcription factors". Genes Dev. 19 (23): 2783–810. doi:10.1101/gad.1350705. PMID 16322555.
9. Wu JW, Hu M, Chai J, Seoane J, Huse M, Li C, Rigotti DJ, Kyin S, Muir TW, Fairman R, Massagué J, Shi Y (December 2001). "Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling". Mol. Cell 8 (6): 1277–89. doi:10.1016/S1097-2765(01)00421-X. PMID 11779503.
10. Shi Y, Hata A, Lo RS, Massagué J, Pavletich NP (July 1997). "A structural basis for mutational inactivation of the tumour suppressor Smad4". Nature 388 (6637): 87–93. doi:10.1038/40431. PMID 9214508.
11. Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (August 2001). "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads". EMBO J. 20 (15): 4132–42. doi:10.1093/emboj/20.15.4132. PMC 149146. PMID 11483516.
12. Sekelsky JJ, Newfeld SJ, Raftery LA, Chartoff EH, Gelbart WM (March 1995). "Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster". Genetics 139(3):1347-58.
13. Savage C, Das P, Finelli AL, Townsend SR, Sun CY, Baird SE, Padgett RW (January 1996). "Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components. Proc. Natl. Acad. Sci. 93(2):790-794.
14. "Gene name - Mothers against dpp". Interactive Fly, Drosophila. Society for Developmental Biology.
15. Hwang J, Mehrani T, Millar SE, Morasso MI (September 2008). "Dlx3 is a crucial regulator of hair follicle differentiation and cycling". Development 135 (18): 3149–59. doi:10.1242/dev.022202. PMC 2707782. PMID 18684741.
16. Park GT, Morasso MI (January 2002). "Bone morphogenetic protein-2 (BMP-2) transactivates Dlx3 through Smad1 and Smad4: alternative mode for Dlx3 induction in mouse keratinocytes". Nucleic Acids Res. 30 (2): 515–22. doi:10.1093/nar/30.2.515. PMC 99823. PMID 11788714.

External links

• Smad Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)