Anks1a regulates COPII-mediated anterograde transport of receptor tyrosine kinases critical for tumorigenesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27619642.
- Also identified by DOI 10.1038/ncomms12799 and PMC identifier 5027278.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
ErbB2 signalling, which is amplified by EphA2 binding, is an important therapeutic target for breast cancer. Despite the importance of the EphA2/ErbB2 complex in promoting breast tumorigenesis, the mechanism by which these receptor tyrosine kinases (RTKs) are exported from the endoplasmic reticulum (ER) remains poorly understood. Here we report that the PTB adaptor Anks1a is specifically localized to the ER on its own serine phosphorylation. Once there, Anks1a acts as an important regulator of COPII-mediated EphA2 ER export. The Anks1a ankyrin repeat domain binds EphA2 and causes it to accumulate at sites of ER exit. Simultaneously, the Anks1a PTB domain binds Sec23. This induces internalization of EphA2 via COPII vesicles, while Anks1a remains behind on the ER membrane. EphA2 also binds ErbB2 in the ER and seems to load ErbB2 into growing COPII carriers. Together, our study reveals a novel mechanism that regulates the loading of RTKs into COPII vesicles.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- COP-Coated Vesicles
- Gene Expression Regulation
- Protein Transport
- Receptor Protein-Tyrosine Kinases