A novel TIP30 protein complex regulates EGF receptor signaling and endocytic degradation |
| |
Authors: | Zhang Chengliang Li Aimin Zhang Xinchun Xiao Hua |
| |
Institution: | Department of Biomedical and Integrative Physiology, Michigan State University, East Lansing, Michigan 48824, USA. |
| |
Abstract: | 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-positive 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. |
| |
Keywords: | Endocytosis Hepatocyte Signal Transduction Trafficking Tumor Suppressor Vesicles EGFR Endophilin B1 Rab5a TIP30 |
本文献已被 PubMed 等数据库收录! |
|