| First Author | Zhang C | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 11 | Pages | 9373-81 |
| PubMed ID | 21252234 | Mgi Jnum | J:170609 |
| Mgi Id | MGI:4946974 | Doi | 10.1074/jbc.M110.207720 |
| Citation | Zhang C, et al. (2011) A Novel TIP30 Protein Complex Regulates EGF Receptor Signaling and Endocytic Degradation. J Biol Chem 286(11):9373-81 |
| abstractText | Activated epidermal growth factor receptor (EGFR) continues to signal in the early endosome, but how this signaling process is regulated is less well understood. Here we describe a protein complex consisting of TIP30, endophilin B1, and acyl-CoA synthetase long chain family member 4 (ACSL4) that interacts with Rab5a and regulates EGFR endocytosis and signaling. These proteins are required for the proper endocytic trafficking of EGF-EGFR. Knockdown of TIP30, ACSL4, endophilin B1, or Rab5a in human liver cancer cells or genetic knock-out of Tip30 in mouse primary hepatocytes results in the trapping of EGF-EGFR complexes in early endosomes, leading to delayed EGFR degradation and prolonged EGFR signaling. Furthermore, we show that Rab5a colocalizes with vacuolar (H(+))-ATPases (V-ATPases) on transport vesicles. The TIP30 complex facilitates trafficking of Rab5a and V-ATPases to EEA1-positve endosomes in response to EGF. Together, these results suggest that this TIP30 complex regulates EGFR endocytosis by facilitating the transport of V-ATPases from trans-Golgi network to early endosomes. |
