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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ren, Jinqi Feng, Shanshan Peränen, Johan Wang, Juanfei Cai, Guoping Guo, Wei Wu, Bin Tuluc, Florin |
| Description | Author Affiliation: Wang J ( School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China); Ren J ( Department of Biology, University of Pennsylvania, Philadelphia, PA 19104); Wu B ( Department of Biology, University of Pennsylvania, Philadelphia, PA 19104); Feng S ( Department of Biology, University of Pennsylvania, Philadelphia, PA 19104); Cai G ( School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China); Tuluc F ( Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104); Peränen J ( Institute of Biotechnology, University of Helsinki, FIN 00014, Helsinki, Finland.); Guo W ( Department of Biology, University of Pennsylvania, Philadelphia, PA 19104); |
| Abstract | Exocytosis is tightly regulated in many cellular processes, from neurite expansion to tumor proliferation. Rab8, a member of the Rab family of small GTPases, plays an important role in membrane trafficking from the trans-Golgi network and recycling endosomes to the plasma membrane. Rabin8 is a guanine nucleotide exchange factor (GEF) and major activator of Rab8. Investigating how Rabin8 is activated in cells is thus pivotal to the understanding of the regulation of exocytosis. Here we show that phosphorylation serves as an important mechanism for Rabin8 activation. We identified Rabin8 as a direct phospho-substrate of ERK1/2 in response to EGF signaling. At the molecular level, ERK phosphorylation relieves the autoinhibition of Rabin8, thus promoting its GEF activity. We further demonstrate that blocking ERK1/2-mediated phosphorylation of Rabin8 inhibits transferrin recycling to the plasma membrane. Together, our results suggest that ERK1/2 activate Rabin8 to regulate vesicular trafficking to the plasma membrane in response to extracellular signaling. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 1 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Epidermal Growth Factor Metabolism Extracellular Signal-Regulated MAP Kinases Guanine Nucleotide Exchange Factors Protein-Serine-Threonine Kinases Signal Transduction Rab GTP-Binding Proteins Amino Acid Sequence Cell Membrane Drug Effects Endocytosis Pharmacology HEK293 Cells HeLa Cells Molecular Sequence Data Phosphorylation Protein Binding Protein Conformation Protein Structure, Tertiary Chemistry Transferrin Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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