TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2
| dc.contributor.author | Hayes, Susan J. | |
| dc.contributor.author | Chawla, Anil | |
| dc.contributor.author | Corvera, Silvia | |
| dc.date | 2022-08-11T08:08:58.000 | |
| dc.date.accessioned | 2022-08-23T16:14:17Z | |
| dc.date.available | 2022-08-23T16:14:17Z | |
| dc.date.issued | 2002-10-03 | |
| dc.date.submitted | 2008-09-25 | |
| dc.identifier.citation | <p>J Cell Biol. 2002 Sep 30;158(7):1239-49.</p> | |
| dc.identifier.issn | 0021-9525 (Print) | |
| dc.identifier.doi | 10.1083/jcb.200204088 | |
| dc.identifier.pmid | 12356868 | |
| dc.identifier.uri | http://hdl.handle.net/20.500.14038/33825 | |
| dc.description.abstract | Transforming growth factor (TGF)beta is an important physiological regulator of cellular growth and differentiation. It activates a receptor threonine/serine kinase that phosphorylates the transcription factor Smad2, which then translocates into the nucleus to trigger specific transcriptional events. Here we show that activated type I and II TGF beta receptors internalize into endosomes containing the early endosomal protein EEA1. The extent of TGF beta-stimulated Smad2 phosphorylation, Smad2 nuclear translocation, and TGF beta-stimulated transcription correlated closely with the extent of internalization of the receptor. TGF beta signaling also requires SARA (Smad anchor for receptor activation), a 135-kD polypeptide that contains a FYVE Zn(++) finger motif. Here we show that SARA localizes to endosomes containing EEA1, and that disruption of this localization inhibits TGF beta-induced Smad2 nuclear translocation. These results indicate that traffic of the TGF beta receptor into the endosome enables TGF beta signaling, revealing a novel function for the endosome as a compartment specialized for the amplification of certain extracellular signals. | |
| dc.language.iso | en_US | |
| dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12356868&dopt=Abstract">Link to article in PubMed</a></p> | |
| dc.relation.url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173232/ | |
| dc.subject | Animals; Binding Sites; COS Cells; Carrier Proteins; Cricetinae; DNA-Binding Proteins; Dynamins; Endosomes; Fluorescent Antibody Technique; Genes, Dominant; Hela Cells; Humans; *Intracellular Signaling Peptides and Proteins; Membrane Proteins; Phosphorylation; Potassium; Protein Transport; Receptors, Transforming Growth Factor beta; *Serine Endopeptidases; Signal Transduction; Smad2 Protein; Subcellular Fractions; Trans-Activators; Transfection; Transferrin; Transforming Growth Factor beta; Tumor Cells, Cultured; Vesicular Transport Proteins; *Zinc Fingers | |
| dc.subject | Life Sciences | |
| dc.subject | Medicine and Health Sciences | |
| dc.title | TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2 | |
| dc.type | Journal Article | |
| dc.source.journaltitle | The Journal of cell biology | |
| dc.source.volume | 158 | |
| dc.source.issue | 7 | |
| dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/gsbs_sp/484 | |
| dc.identifier.contextkey | 638252 | |
| html.description.abstract | <p>Transforming growth factor (TGF)beta is an important physiological regulator of cellular growth and differentiation. It activates a receptor threonine/serine kinase that phosphorylates the transcription factor Smad2, which then translocates into the nucleus to trigger specific transcriptional events. Here we show that activated type I and II TGF beta receptors internalize into endosomes containing the early endosomal protein EEA1. The extent of TGF beta-stimulated Smad2 phosphorylation, Smad2 nuclear translocation, and TGF beta-stimulated transcription correlated closely with the extent of internalization of the receptor. TGF beta signaling also requires SARA (Smad anchor for receptor activation), a 135-kD polypeptide that contains a FYVE Zn(++) finger motif. Here we show that SARA localizes to endosomes containing EEA1, and that disruption of this localization inhibits TGF beta-induced Smad2 nuclear translocation. These results indicate that traffic of the TGF beta receptor into the endosome enables TGF beta signaling, revealing a novel function for the endosome as a compartment specialized for the amplification of certain extracellular signals.</p> | |
| dc.identifier.submissionpath | gsbs_sp/484 | |
| dc.contributor.department | Program in Molecular Medicine | |
| dc.contributor.department | Morningside Graduate School of Biomedical Sciences | |
| dc.source.pages | 1239-49 | |
| dc.description.thesisprogram | Interdisciplinary Graduate Program |
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