Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor β and activin Journal Article
| Authors: | Cárcamo, J.; Weis, F. M. B.; Ventura, F.; Wieser, R.; Wrana, J. L.; Attisano, L.; Massagué, J. |
| Article Title: | Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor β and activin |
| Abstract: | Transforming growth factor β (TGF-β) and activin bind to receptor complexes that contain two distantly related transmembrane serine/threonine kinases known as receptor types I and II. The type II receptors determine ligand binding specificity, and each interacts with a distinct repertoire of type I receptors. Here we identify a new type I receptor for activin, ActR- IB, whose kinase domain is nearly identical to that of the recently cloned TGF-β type I receptor, TβR-I. ActR-IB has the structural and binding properties of a type I receptor: it binds activin only in the presence of an activin type II receptor and forms a heteromeric noncovalent complex with activin type II receptors. In Mv1Lu lung epithelial cells, ActR-IB and TβR- I signal a common set of growth-inhibitory and transcriptional responses in association with their corresponding ligands and type II receptors. The transcriptional responses include elevated expression of fibronectin and plasminogen activator inhibitor 1. Although TβR-I and ActR-IB are nearly identical in their kinase domains (90% amino acid sequence identity), their corresponding type II receptor kinase domains are very different from each other (42% amino acid sequence identity). Therefore, signaling of a specific set of responses by TGF-β and activin correlates with the presence of similar type I kinases in their complex. Indeed, other TGF-β and activin type I receptors (TSR-I and ActR-I) whose kinase domains significantly diverge from those of TβR-I and ActR-IB do not substitute as mediators of these growth-inhibitory and extracellular matrix transcriptional responses. Hence, we conclude that the type I receptor subunits are primary specifiers of signals sent by TGF-β and activin receptor complexes. |
| Keywords: | sequence analysis; nonhuman; comparative study; binding affinity; polymerase chain reaction; animal cell; animal; cell division; gene expression; transforming growth factor beta; cell line; luciferase; transcription, genetic; transfection; cercopithecus aethiops; animalia; kidney; transcription regulation; amino acid sequence; molecular sequence data; sequence homology, amino acid; protein synthesis; lung; receptors, transforming growth factor beta; base sequence; dna primers; sequence homology; mutagenesis; swine; receptor binding; dna, complementary; mink; growth inhibition; fibronectin; receptors, growth factor; receptor subtype; growth factor receptor; lung alveolus epithelium; activin receptors, type i; activin; activins; human; priority journal; article; inhibins; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; activin receptors; plasminogen activator inhibitor |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 14 |
| Issue: | 6 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 1994-06-01 |
| Start Page: | 3810 |
| End Page: | 3821 |
| Language: | English |
| PROVIDER: | scopus |
| PMCID: | PMC358748 |
| PUBMED: | 8196624 |
| DOI: | 10.1128/MCB.14.6.3810 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- CODEN: MCEBD C2 -- Source: Scopus |
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