- SMAD (protein)
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SMADs are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus where they activate downstream TGF-β 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]
Contents
Classes
There are three classes of SMAD:
- The receptor-regulated Smads (R-SMAD) which include SMAD1, SMAD2, SMAD3, SMAD5 and SMAD8/9[9]
- The common-mediator Smad (co-SMAD) which includes only SMAD4, which interacts with R-SMADs to participate in signaling[10]
- 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) and the Caenorhabditis 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.
References
- ^ 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.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0955-0674(98)80141-5.
- ^ Massagué J (1998). "TGF-beta signal transduction". Annu. Rev. Biochem. 67: 753–91. doi:10.1146/annurev.biochem.67.1.753. PMID 9759503.
- ^ 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.
- ^ 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. http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=9716398.
- ^ Wrana JL (March 2000). "Crossing Smads". Sci. STKE 2000 (23): RE1. doi:10.1126/stke.2000.23.re1. PMID 11752591.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0092-8674(00)81696-7.
- ^ Massagué J, Seoane J, Wotton D (December 2005). "Smad transcription factors". Genes Dev. 19 (23): 2783–810. doi:10.1101/gad.1350705. PMID 16322555.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S1097-2765(01)00421-X.
- ^ 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.
- ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149146.
External links
Cell signaling: carrier proteins: signal transducing adaptor proteins JAK-STAT Growth factor receptor-bound protein Other Cell signaling: TGF beta signaling pathway 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 and inhibin, Anti-müllerian hormone, Nodal)TGF beta receptors
(Activin, BMP)TGFBR1: Activin type 1 receptors (ACVR1, ACVR1B, ACVR1C) · ACVRL1 · BMPR1 (BMPR1A · BMPR1B)
TGFBR2: Activin type 2 receptors (ACVR2A, ACVR2B) · AMHR2 · BMPR2
TGFBR3: betaglycanTransducers/SMAD Ligand inhibitors Coreceptors Other SARATranscription factors and intracellular receptors (1) Basic domains (1.1) Basic leucine zipper (bZIP)Activating transcription factor (AATF, 1, 2, 3, 4, 5, 6, 7) · AP-1 (c-Fos, FOSB, FOSL1, FOSL2, JDP2, c-Jun, JUNB, JUND) · BACH (1, 2) · BATF · BLZF1 · C/EBP (α, β, γ, δ, ε, ζ) · CREB (1, 3, L1) · CREM · DBP · DDIT3 · GABPA · HLF · MAF (B, F, G, K) · NFE (2, L1, L2, L3) · NFIL3 · NRL · NRF (1, 2, 3) · XBP1(1.2) Basic helix-loop-helix (bHLH)ATOH1 · AhR · AHRR · ARNT · ASCL1 · BHLHB2 · BMAL (ARNTL, ARNTL2) · CLOCK · EPAS1 · FIGLA · HAND (1, 2) · HES (5, 6) · HEY (1, 2, L) · HES1 · HIF (1A, 3A) · ID (1, 2, 3, 4) · LYL1 · MESP2 · MXD4 · MYCL1 · MYCN · Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) · Neurogenins (1, 2, 3) · NeuroD (1, 2) · NPAS (1, 2, 3) · OLIG (1, 2) · Pho4 · Scleraxis · SIM (1, 2) · TAL (1, 2) · Twist · USF1(1.3) bHLH-ZIP(1.4) NF-1(1.5) RF-X(1.6) Basic helix-span-helix (bHSH)(2) Zinc finger DNA-binding domains (2.1) Nuclear receptor (Cys4)subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR)
subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX)
subfamily 3 (Steroid hormone (Androgen, Estrogen (α, β), Glucocorticoid, Mineralocorticoid, Progesterone), Estrogen related (α, β, γ))
subfamily 4 NUR (NGFIB, NOR1, NURR1) · subfamily 5 (LRH-1, SF1) · subfamily 6 (GCNF) · subfamily 0 (DAX1, SHP)(2.2) Other Cys4(2.3) Cys2His2General transcription factors (TFIIA, TFIIB, TFIID, TFIIE (1, 2), TFIIF (1, 2), TFIIH (1, 2, 4, 2I, 3A, 3C1, 3C2))
ATBF1 · BCL (6, 11A, 11B) · CTCF · E4F1 · EGR (1, 2, 3, 4) · ERV3 · GFI1 · GLI-Krüppel family (1, 2, 3, REST, S2, YY1) · HIC (1, 2) · HIVEP (1, 2, 3) · IKZF (1, 2, 3) · ILF (2, 3) · KLF (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17) · MTF1 · MYT1 · OSR1 · PRDM9 · SALL (1, 2, 3, 4) · SP (1, 2, 4, 7, 8) · TSHZ3 · WT1 · Zbtb7 (7A, 7B) · ZBTB (16, 17, 20, 32, 33, 40) · zinc finger (3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 300, 318, 330, 346, 350, 365, 366, 384, 423, 451, 452, 471, 593, 638, 644, 649, 655)(2.4) Cys6(2.5) Alternating composition(3) Helix-turn-helix domains (3.1) HomeodomainARX · CDX (1, 2) · CRX · CUTL1 · DBX (1, 2) · DLX (3, 4, 5) · EMX2 · EN (1, 2) · FHL (1, 2, 3) · HESX1 · HHEX · HLX · Homeobox (A1, A2, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C12, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) · HOPX · IRX (1, 2, 3, 4, 5, 6, MKX) · LMX (1A, 1B) · MEIS (1, 2) · MEOX2 · MNX1 · MSX (1, 2) · NANOG · NKX (2-1, 2-2, 2-3, 2-5, 3-1, 3-2, 6-1, 6-2) · NOBOX · PBX (1, 2, 3) · PHF (1, 3, 6, 8, 10, 16, 17, 20, 21A) · PHOX (2A, 2B) · PITX (1, 2, 3) · POU domain (PIT-1, BRN-3: A, B, C, Octamer transcription factor: 1, 2, 3/4, 6, 7, 11) · OTX (1, 2) · PDX1 · SATB2 · SHOX2 · VAX1 · ZEB (1, 2)(3.2) Paired box(3.3) Fork head / winged helix(3.4) Heat Shock Factors(3.5) Tryptophan clusters(3.6) TEA domain(4) β-Scaffold factors with minor groove contacts (4.1) Rel homology region(4.2) STAT(4.3) p53(4.4) MADS box(4.6) TATA binding proteins(4.7) High-mobility group(4.10) Cold-shock domainCSDA, YBX1(4.11) Runt(0) Other transcription factors (0.2) HMGI(Y)(0.3) Pocket domain(0.6) MiscellaneousCategories:- Transcription factors
- SMAD
- Molecular and cellular biology stubs
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