Definition: MAD proteins (MADHs or SMADs), originally defined in Drosophila, are essential components of the signaling pathways of the transforming growth factor-beta receptor family (TGFBs).
Ligands of the transforming growth factor-beta (TGFbeta) superfamily of growth factors initiate signal transduction through a bewildering complexity of ligand-receptor interactions.
Signalling then converges to nuclear accumulation of transcriptionally active SMAD complexes and gives rise to a plethora of specific functional responses in both embryos and adult organisms.
Function
Members of the TGF-beta superfamily of growth factors (TGFB superfamily) mediate their effects through activation of intracellular Smad proteins (MADHs), which form transcriptionally competent complexes that accumulate in the nucleus.
Smads actively shuttle between the cytoplasm and nucleus by distinct mechanisms.
Members
| MADH1 | MADH2 | MADH3 | MADH4 | MADH5 | MADH6 | MADH7 |
| SMAD1 | SMAD2 | SMAD3 | SMAD4 | SMAD5 | SMAD6 | SMAD7 |
Features
TGFbeta signaling pathway
References
Schmierer B, Hill CS. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 2007 Dec;8(12):970-82. PMID: 18000526
Reguly T, Wrana JL. In or out? The dynamics of Smad nucleocytoplasmic shuttling. Trends Cell Biol. 2003 May;13(5):216-20. PMID: 12742164
Miyazawa K, Shinozaki M, Hara T, Furuya T, Miyazono K. Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells. 2002 Dec;7(12):1191-204. PMID: 12485160
Souchelnytskyi S, Moustakas A, Heldin CH. TGF-beta signaling from a three-dimensional perspective: insight into selection of partners. Trends Cell Biol. 2002 Jul;12(7):304-7. PMID: 12185845
Attisano L, Tuen Lee-Hoeflich S. The Smads. Genome Biol. 2001;2(8):REVIEWS3010. Epub 2001 Aug 2. PMID: 11532220