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Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor
| Content Provider | Semantic Scholar |
|---|---|
| Author | Hanafusa, Hiroshi Ishikawa, Kouki Kedashiro, Shin Saigo, Tsukasa Iemura, Shun-Ichiro Natsume, Tohru Komada, Masayuki Shibuya, Hiroshi Nara, Atsuki Matsumoto, Kunihiro |
| Copyright Year | 2011 |
| Abstract | Activation of the epidermal growth factor receptor (EGFR) not only initiates multiple signal-transduction pathways, including the MAP kinase (MAPK) pathway, but also triggers trafficking events that relocalize receptors from the cell surface to intracellular endocytic compartments. In this paper, we demonstrate that leucine-rich repeat kinase LRRK1, which contains a MAPKKK-like kinase domain, forms a complex with activated EGFR through an interaction with Grb2. Subsequently, LRRK1 and epidermal growth factor (EGF) are internalized and co-localized in early endosomes. LRRK1 regulates EGFR transport from early to late endosomes and regulates the motility of EGF-containing early endosomes in a manner dependent on its kinase activity. Furthermore, LRRK1 serves as a scaffold facilitating the interaction of EGFR with the endosomal sorting complex required for transport-0 complex, thus enabling efficient sorting of EGFR to the inner vesicles of multivesicular bodies. Our findings provide the first evidence that a MAPKKK-like protein regulates the endosomal trafficking of EGFR. |
| Starting Page | 158 |
| Ending Page | 158 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 21245839 |
| Volume Number | 2 |
| Journal | Nature communications |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Anatomical compartments EGF gene Endosomes Epidermal Growth Factor Receptor Growth Factor Receptors LRRK1 gene Leucine Leucine-Rich Repeat Mitogen-Activated Protein Kinases Multivesicular body Precipitating Factors Small Leucine-Rich Proteoglycans Vesicle (morphologic abnormality) kinase activity transduction |
| Content Type | Text |
| Resource Type | Article |
