| First Author | Hao X | Year | 2011 |
| Journal | Cell Signal | Volume | 23 |
| Issue | 5 | Pages | 935-46 |
| PubMed ID | 21266196 | Mgi Jnum | J:205663 |
| Mgi Id | MGI:5545984 | Doi | 10.1016/j.cellsig.2011.01.022 |
| Citation | Hao X, et al. (2011) SNX25 regulates TGF-beta signaling by enhancing the receptor degradation. Cell Signal 23(5):935-46 |
| abstractText | SNXs (sorting nexin), a family of proteins playing roles in cargo sorting and signaling from compartments within the endocytic network, regulate traffic of membrane proteins including TGF-beta receptors. Here we report that the full length human and mouse SNX25, a SNX member with PX, PXA and RGS domains, co-localizes with TGF-beta receptors, and forms internalized cytosolic punctae upon treatment with TGF-beta. While overexpression of SNX25 inhibits TGF-beta induced luciferase reporter activity, knocking down endogenous SNX25 by siRNA in NIH3T3 cells elevates the TGF-beta receptor levels and facilitates TGF-beta signaling. Immunoprecipitation experiments demonstrate that SNX25 interacts with TbetaRI. Western blot analyses indicate that SNX25 enhances the degradation of TGF-beta receptors. SNX25 induced TGF-beta receptor degradation is shown via the clathrin dependent endocytosis pathway into lysosome. We have characterized that PXA domain of SNX25 is required for the degradation of TbetaRI. Our findings demonstrate that SNX25 negatively regulates TGF-beta signaling by enhancing the receptor degradation through lysosome pathway. |