Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Genes Dev
1998 Jul 15;1214:2144-52. doi: 10.1101/gad.12.14.2144.
Show Gene links
Show Anatomy links
Determinants of specificity in TGF-beta signal transduction.
Chen YG, Hata A, Lo RS, Wotton D, Shi Y, Pavletich N, Massagué J.
???displayArticle.abstract???
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.
???displayArticle.pubmedLink???
9679059 ???displayArticle.pmcLink???PMC317013 ???displayArticle.link???Genes Dev
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
