Signaling activity of transforming growth factor β type II receptors lacking specific domains in the cytoplasmic region Journal Article
| Authors: | Wieser, R.; Attisano, L.; Wrana, J. L.; Massagué, J. |
| Article Title: | Signaling activity of transforming growth factor β type II receptors lacking specific domains in the cytoplasmic region |
| Abstract: | The transforming growth factor β (TGF-β) type II receptor (TβR-II) is a transmembrane serine/threonine kinase that contains two inserts in the kinase region and a serine/threonine-rich C-terminal extension. TβR-II is required for TGF-β binding to the type I receptor, with which it forms a heteromeric receptor complex, and its kinase activity is required for signaling by this complex. We investigated the role of various cytoplasmic regions in TβR-II by altering or deleting these regions and determining the signaling activity of the resulting products in cell lines made resistant to TGF-β by inactivation of the endogenous TβR-II. TGF-β binding to receptor I and responsiveness to TGF-β in these cells can be restored by transfection of wild-type TβR-II. Using this system, we show that the kinase insert 1 and the C-terminal tail of TβR-II, in contrast to the corresponding regions in most tyrosine kinase receptors, are not essential to specify ligand-induced responses. Insert 2 is necessary to support the catalytic activity of the receptor kinase, and its deletion yields a receptor that is unable to mediate any of the responses tested. However, substitution of this insert with insert 2 from the activin receptor, ActR-IIB, does not diminish the ability of TβR- II to elicit these responses. A truncated TβR-II lacking the cytoplasmic domain still binds TGF-β, supports ligand binding to receptor I, and forms a complex with this receptor. However, TGF-β binding to receptor I facilitated by this truncated TβR-II fails to inhibit cell proliferation, activate extracellular matrix protein production, or activate transcription from a promoter containing TGF-β-responsive elements. We conclude that the transcriptional and antiproliferative responses to TGF-β require both components of a heteromeric receptor complex that differs from tyrosine kinase receptors in its mode of signaling. |
| Keywords: | signal transduction; sequence deletion; nonhuman; polymerase chain reaction; cell proliferation; animal cell; animal; cell division; transforming growth factor beta; carboxy terminal sequence; cell line; protein; transcription, genetic; enzyme activity; protein serine threonine kinase; phosphorylation; dna; amino acid sequence; molecular sequence data; hybrid protein; genetic transfection; protein-serine-threonine kinases; immunoprecipitation; receptors, transforming growth factor beta; cytoplasm; base sequence; binding site; amino acid; adenosine triphosphate; mutagenesis; autoradiography; concentration response; receptor binding; polyacrylamide gel electrophoresis; mink; fibronectin; transforming growth factor beta2; regulator gene; growth factor receptor; activin; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 13 |
| Issue: | 12 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 1993-12-01 |
| Start Page: | 7239 |
| End Page: | 7247 |
| Language: | English |
| PUBMED: | 8246946 |
| PROVIDER: | scopus |
| PMCID: | PMC364794 |
| DOI: | 10.1128/MCB.13.12.7239 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
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