Distinct oligomeric states of SMAD proteins in the transforming growth factor-β pathway Journal Article

  


Authors: Jayaraman, L.; Massagué, J.
Article Title: Distinct oligomeric states of SMAD proteins in the transforming growth factor-β pathway
Abstract: Protein interactions are critical for the function of SMADs as mediators of transforming growth factor-β (TGF-β) signals. TGF-β receptor phosphorylation of SMAD2 or SMAD3 causes their association with SMAD4 and accumulation in the nucleus where the SMAD complex binds cofactors that determine the choice of target genes. We provide evidence that in the basal state, SMADs 2, 3, and 4 form separate, strikingly different complexes. SMAD2 is found mostly as monomer, whereas the closely related SMAD3 exists in multiple oligomeric states. This difference is due to a unique structural element in the MH1 domain of SMAD2 that inbibits protein-protein interactions in the basal state. In contrast to SMAD2 and SMAD3, SMAD4 in the basal state is found mostly as a homo-oligomer, most likely a trimer. Upon cell stimulation with TGF-β, SMAD proteins become engaged in a multitude of complexes ranging in size from SMAD2-SMAD4 heterodimers to assemblies of >650 kDa. The latter display the highest DNA binding affinity for the TGF-β-response elements of JUNB and collagen 7. These observations, all validated with endogenous SMAD proteins, modify previous models regarding the assembly and activity of SMAD complexes in the TGF-β pathway.
Keywords: signal transduction; controlled study; protein phosphorylation; unclassified drug; oncoprotein; dna-binding proteins; nonhuman; protein domain; animal cell; animals; complex formation; smad protein; smad2 protein; smad3 protein; transforming growth factor beta; protein assembly; protein dna binding; protein protein interaction; cos cells; animalia; dna; dimerization; response elements; trans-activators; monkey; oligomerization; smad4 protein; oligomer; priority journal; article; collagen type 7; oncogene c jun
Journal Title: Journal of Biological Chemistry
Volume: 275
Issue: 52
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2000-12-29
Start Page: 40710
End Page: 40717
Language: English
DOI: 10.1074/jbc.M005799200
PUBMED: 11018029
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0034731334&partnerID=40&md5=5fa914d295c3801faa07e246ff922954
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Joan Massague
    388 Massague
  2. Lata Jayaraman
    3 Jayaraman
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