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Transforming growth factor–β (TGF-β)–induced up-regulation of TGF-β receptors at the cell surface amplifies the TGF-β response
| Content Provider | Scilit |
|---|---|
| Author | Duan, Dana Derynck, Rik |
| Copyright Year | 2019 |
| Description | Journal: Journal of Biological Chemistry Functional activation of the transforming growth factor–β (TGF-β) receptors (TGFBRs) is carefully regulated through integration of post-translational modifications, spatial regulation at the cellular level, and TGFBR availability at the cell surface. Although the bulk of TGFBRs resides inside the cells, AKT Ser/Thr kinase (AKT) activation in response to insulin or other growth factors rapidly induces transport of TGFBRs to the cell surface, thereby increasing the cell's responsiveness to TGF-β. We now demonstrate that TGF-β itself induces a rapid translocation of its own receptors to the cell surface and thus amplifies its own response. This mechanism of response amplification, which hitherto has not been reported for other cell-surface receptors, depended on AKT activation and TGF-β type I receptor kinase. In addition to an increase in cell-surface TGFBR levels, TGF-β treatment promoted TGFBR internalization, suggesting an overall amplification of TGFBR cycling. The TGF-β–induced increase in receptor presentation at the cell surface amplified TGF-β–induced SMAD family member (SMAD) activation and gene expression. Furthermore, bone morphogenetic protein 4 (BMP-4), which also induces AKT activation, increased TGFBR levels at the cell surface, leading to enhanced autocrine activation of TGF-β–responsive SMADs and gene expression, providing context for the activation of TGF-β signaling in response to BMP during development. In summary, our results indicate that TGF-β– and BMP-induced activation of low levels of cell surface–associated TGFBRs rapidly mobilizes additional TGFBRs from intracellular stores to the cell surface, increasing the abundance of cell-surface TGFBRs and cells' responsiveness to TGF-β signaling. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544840/pdf http://www.jbc.org/content/294/21/8490.full.pdf |
| Ending Page | 8504 |
| Page Count | 15 |
| Starting Page | 8490 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.ra118.005763 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 21 |
| Volume Number | 294 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2019-05-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Akt Pkb Smad Transcription Factor Smad Activation Autocrine Signaling Bone Morphogenetic Protein (bmp) Cell-surface Receptor Transcription Regulation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
