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Genes Dev
1998 Jul 15;1214:2144-52. doi: 10.1101/gad.12.14.2144.
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Determinants of specificity in TGF-beta signal transduction.
Chen YG
,
Hata A
,
Lo RS
,
Wotton D
,
Shi Y
,
Pavletich N
,
Massagué J
.
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Signal transduction by the TGF-beta family involves sets of receptor serine/threonine kinases, Smad proteins that act as receptor substrates, and Smad-associated transcription factors that target specific genes. We have identified discrete structural elements that dictate the selective interactions between receptors and Smads and between Smads and transcription factors in the TGF-beta and BMP pathways. A cluster of four residues in the L45 loop of the type I receptor kinase domain, and a matching set of two residues in the L3 loop of the Smad carboxy-terminal domain establish the specificity of receptor-Smad interactions. A cluster of residues in the highly exposed alpha-helix 2 of the Smad carboxy-terminal domain specify the interaction with the DNA-binding factor Fast1 and, as a result, the gene responses mediated by the pathway. By establishing specific interactions, these determinants keep the TGF-beta and BMP pathways segregated from each other.
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9679059
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Baker,
A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway.
1996, Pubmed,
Xenbase
Baker,
A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway.
1996,
Pubmed
,
Xenbase
Candia,
Cellular interpretation of multiple TGF-beta signals: intracellular antagonism between activin/BVg1 and BMP-2/4 signaling mediated by Smads.
1997,
Pubmed
,
Xenbase
Cárcamo,
Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin.
1994,
Pubmed
Cárcamo,
Disruption of transforming growth factor beta signaling by a mutation that prevents transphosphorylation within the receptor complex.
1995,
Pubmed
Cheifetz,
Distinct transforming growth factor-beta (TGF-beta) receptor subsets as determinants of cellular responsiveness to three TGF-beta isoforms.
1990,
Pubmed
Chen,
Transcriptional regulation by transforming growth factor beta of the expression of retinoic acid and retinoid X receptor genes in osteoblastic cells is mediated through AP-1.
1996,
Pubmed
Chen,
Smad8 mediates the signaling of the ALK-2 [corrected] receptor serine kinase.
1997,
Pubmed
,
Xenbase
Chen,
Mechanism of TGFbeta receptor inhibition by FKBP12.
1997,
Pubmed
Chen,
Smad4 and FAST-1 in the assembly of activin-responsive factor.
1997,
Pubmed
,
Xenbase
Chen,
A transcriptional partner for MAD proteins in TGF-beta signalling.
1996,
Pubmed
,
Xenbase
Feng,
A kinase subdomain of transforming growth factor-beta (TGF-beta) type I receptor determines the TGF-beta intracellular signaling specificity.
1997,
Pubmed
Gaddy-Kurten,
Activins and the receptor serine kinase superfamily.
1995,
Pubmed
Graff,
Xenopus Mad proteins transduce distinct subsets of signals for the TGF beta superfamily.
1996,
Pubmed
,
Xenbase
Hahn,
DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1.
1996,
Pubmed
Hata,
Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4.
1997,
Pubmed
,
Xenbase
Hata,
Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor.
1998,
Pubmed
,
Xenbase
Heldin,
TGF-beta signalling from cell membrane to nucleus through SMAD proteins.
1997,
Pubmed
Hogan,
Bone morphogenetic proteins: multifunctional regulators of vertebrate development.
1996,
Pubmed
Hoodless,
MADR1, a MAD-related protein that functions in BMP2 signaling pathways.
1996,
Pubmed
Huang,
Identification of a potential regulator of early transcriptional responses to mesoderm inducers in the frog embryo.
1995,
Pubmed
,
Xenbase
Kingsley,
The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms.
1994,
Pubmed
Kretzschmar,
Opposing BMP and EGF signalling pathways converge on the TGF-beta family mediator Smad1.
1997,
Pubmed
Kretzschmar,
The TGF-beta family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase.
1997,
Pubmed
Lagna,
Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways.
1996,
Pubmed
,
Xenbase
Liu,
A human Mad protein acting as a BMP-regulated transcriptional activator.
1996,
Pubmed
,
Xenbase
Liu,
Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes.
1997,
Pubmed
,
Xenbase
Lo,
The L3 loop: a structural motif determining specific interactions between SMAD proteins and TGF-beta receptors.
1998,
Pubmed
Macías-Silva,
MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling.
1996,
Pubmed
Massagué,
The transforming growth factor-beta family.
1990,
Pubmed
Massagué,
TGF-beta signal transduction.
1998,
Pubmed
Mehler,
Bone morphogenetic proteins in the nervous system.
1997,
Pubmed
Nagatake,
Somatic in vivo alterations of the DPC4 gene at 18q21 in human lung cancers.
1996,
Pubmed
Nakao,
TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4.
1997,
Pubmed
,
Xenbase
Pawson,
Signaling through scaffold, anchoring, and adaptor proteins.
1997,
Pubmed
Savage,
Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components.
1996,
Pubmed
Sekelsky,
Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster.
1995,
Pubmed
Shi,
A structural basis for mutational inactivation of the tumour suppressor Smad4.
1997,
Pubmed
Suzuki,
Smad5 induces ventral fates in Xenopus embryo.
1997,
Pubmed
,
Xenbase
Taylor,
Structural framework for the protein kinase family.
1992,
Pubmed
ten Dijke,
Characterization of type I receptors for transforming growth factor-beta and activin.
1994,
Pubmed
Thomsen,
Xenopus mothers against decapentaplegic is an embryonic ventralizing agent that acts downstream of the BMP-2/4 receptor.
1996,
Pubmed
,
Xenbase
Weis-Garcia,
Complementation between kinase-defective and activation-defective TGF-beta receptors reveals a novel form of receptor cooperativity essential for signaling.
1996,
Pubmed
Wieser,
GS domain mutations that constitutively activate T beta R-I, the downstream signaling component in the TGF-beta receptor complex.
1995,
Pubmed
Wrana,
TGF beta signals through a heteromeric protein kinase receptor complex.
1992,
Pubmed
Wrana,
Mechanism of activation of the TGF-beta receptor.
1994,
Pubmed
Wu,
Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4.
1997,
Pubmed
Yingling,
Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth.
1996,
Pubmed
Zhang,
Receptor-associated Mad homologues synergize as effectors of the TGF-beta response.
1996,
Pubmed
