Determinants of specificity in TGF-β signal transduction Journal Article
| Authors: | Chen, Y. G.; Hata, A.; Lo, R. S.; Wotton, D.; Shi, Y.; Pavletich, N.; Massagué, J. |
| Article Title: | Determinants of specificity in TGF-β signal transduction |
| Abstract: | Signal transduction by the TGF-β 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-β 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 α-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-β and BMP pathways segregated from each other. |
| Keywords: | signal transduction; controlled study; dna binding protein; human cell; dna-binding proteins; nonhuman; protein domain; forkhead transcription factors; animal cell; animals; bone morphogenetic protein; smad2 protein; smad3 protein; transforming growth factor beta; carboxy terminal sequence; protein protein interaction; transcription factor; tumor cells, cultured; protein serine threonine kinase; cos cells; animalia; transcription factors; amino acid sequence; molecular sequence data; protein-serine-threonine kinases; cell strain cos1; receptors, transforming growth factor beta; smad proteins; binding sites; trans-activators; xenopus; receptor protein; xenopus proteins; tgf-β; activin receptors, type i; humans; human; priority journal; article; bmp pathway |
| Journal Title: | Genes and Development |
| Volume: | 12 |
| Issue: | 14 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 1998-07-15 |
| Start Page: | 2144 |
| End Page: | 2152 |
| Language: | English |
| PUBMED: | 9679059 |
| PROVIDER: | scopus |
| PMCID: | PMC317013 |
| DOI: | 10.1101/gad.12.14.2144 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work