Smad1 recognition and activation by the ALK1 group of transforming growth factor-β family receptors Journal Article
| Authors: | Chen, Y. G.; Massagué, J. |
| Article Title: | Smad1 recognition and activation by the ALK1 group of transforming growth factor-β family receptors |
| Abstract: | Two structural elements, the L45 loop on the kinase domain of the transforming growth factor-β (TGF-β) family type I receptors and the L3 loop on the MH2 domain of Smad proteins, determine the specificity of the interactions between these receptors and Smad proteins. The L45 sequence of the TGF-β type I receptor (TβR-I) specifies Smad2 interaction, whereas the related L45 sequence of the bone morphogenetic protein (BMP) type I receptor (BMPR-I) specifies Smad1 interactions. Here we report that members of a third receptor group, which includes ALK1 and ALK2 from vertebrates and Saxophone from Drosophila, specifically phosphorylate and activate Smad1 even though the L45 sequence of this group is very divergent from that of BMPR-I. We investigated the structural elements that determine the specific recognition of Smad1 by ALK1 and ALK2. In addition to the receptor L45 loop and the Smad1 L3 loop, the specificity of this recognition requires the α-helix 1 of Smad1. The α-helix 1 is a conserved structural element located in the vicinity of the L3 loop on the surface of the Smad MH2 domain. Thus, Smad1 recognizes two distinct groups of receptors, the BMPR-I group and the ALK1 group, through different L45 sequences on the receptor kinase domain and a differential use of two surface structures on the Smad1 MH2 domain. |
| Keywords: | signal transduction; protein phosphorylation; dna-binding proteins; nonhuman; mutant protein; animals; bone morphogenetic protein; smad1 protein; protein protein interaction; cell line; protein binding; drosophila; cos cells; phosphorylation; vertebrata; enzyme phosphorylation; amino acid sequence; molecular sequence data; transforming growth factor beta receptor; receptors, transforming growth factor beta; smad proteins; cellular distribution; models, molecular; binding sites; trans-activators; enzyme specificity; activin; humans; priority journal; article |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 274 |
| Issue: | 6 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1999-02-05 |
| Start Page: | 3672 |
| End Page: | 3677 |
| Language: | English |
| DOI: | 10.1074/jbc.274.6.3672 |
| PUBMED: | 9920917 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work