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A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3.
Oncogene. 1999 Feb 25; 18(8):1643-8.O

Abstract

Smad proteins are essential components of the signalling cascade initiated by members of the Transforming Growth Factor-beta family. TGFbeta binding to heteromeric complexes of transmembrane Ser/Thr kinases induces Smad2 and Smad3 phosphorylation on their C terminus residues. This phosphorylation leads to oligomerization with Smad4, a common mediator of TGF-beta, activin and BMP signalling. The Smad complexes then translocate to the nucleus where they play transcription regulator roles. Even if they share 92% identity, the two TGFbeta/ restricted Smad2 and Smad3 are not functionally equivalent. As we have previously shown, Smad3 acts as a transcription factor by binding to a TGFbeta-responsive sequence termed CAGA box whereas Smad2 does not. Smad2 differs from Smad3 mainly in the N-terminal MH1 domain where it contains two additional stretches of amino acids that are lacking in Smad3. Here, we show that one of these domains corresponding to exon 3 is responsible for the absence of Smad2 transcriptional activity in CAGA box-containing promoters. Furthermore, in vitro studies indicate that this domain prevents Smad2 from binding to this DNA sequence. This suggests that Smad2 and Smad3 may have different subsets of target genes participating thus in distinct responses among TGFbeta pleiotropic effects.

Authors+Show Affiliations

Laboratoire Glaxo Wellcome, LES ULIS, France.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

10102636

Citation

Dennler, S, et al. "A Short Amino-acid Sequence in MH1 Domain Is Responsible for Functional Differences Between Smad2 and Smad3." Oncogene, vol. 18, no. 8, 1999, pp. 1643-8.
Dennler S, Huet S, Gauthier JM. A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3. Oncogene. 1999;18(8):1643-8.
Dennler, S., Huet, S., & Gauthier, J. M. (1999). A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3. Oncogene, 18(8), 1643-8.
Dennler S, Huet S, Gauthier JM. A Short Amino-acid Sequence in MH1 Domain Is Responsible for Functional Differences Between Smad2 and Smad3. Oncogene. 1999 Feb 25;18(8):1643-8. PubMed PMID: 10102636.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3. AU - Dennler,S, AU - Huet,S, AU - Gauthier,J M, PY - 1999/4/2/pubmed PY - 1999/4/2/medline PY - 1999/4/2/entrez SP - 1643 EP - 8 JF - Oncogene JO - Oncogene VL - 18 IS - 8 N2 - Smad proteins are essential components of the signalling cascade initiated by members of the Transforming Growth Factor-beta family. TGFbeta binding to heteromeric complexes of transmembrane Ser/Thr kinases induces Smad2 and Smad3 phosphorylation on their C terminus residues. This phosphorylation leads to oligomerization with Smad4, a common mediator of TGF-beta, activin and BMP signalling. The Smad complexes then translocate to the nucleus where they play transcription regulator roles. Even if they share 92% identity, the two TGFbeta/ restricted Smad2 and Smad3 are not functionally equivalent. As we have previously shown, Smad3 acts as a transcription factor by binding to a TGFbeta-responsive sequence termed CAGA box whereas Smad2 does not. Smad2 differs from Smad3 mainly in the N-terminal MH1 domain where it contains two additional stretches of amino acids that are lacking in Smad3. Here, we show that one of these domains corresponding to exon 3 is responsible for the absence of Smad2 transcriptional activity in CAGA box-containing promoters. Furthermore, in vitro studies indicate that this domain prevents Smad2 from binding to this DNA sequence. This suggests that Smad2 and Smad3 may have different subsets of target genes participating thus in distinct responses among TGFbeta pleiotropic effects. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/10102636/A_short_amino_acid_sequence_in_MH1_domain_is_responsible_for_functional_differences_between_Smad2_and_Smad3_ L2 - https://doi.org/10.1038/sj.onc.1202729 DB - PRIME DP - Unbound Medicine ER -