Activated ErbB3 Translocates to the Nucleus via Clathrin-independent Endocytosis, Which Is Associated with Proliferating Cells.
J Biol Chem
; 291(8): 3837-47, 2016 Feb 19.
Article
in En
| MEDLINE
| ID: mdl-26719328
ABSTRACT
Members of the receptor tyrosine kinase family (RTK) have been shown to be present in the nucleus of cells; however, the mechanisms underlying their trafficking to the nucleus, and their relevance once there are poorly understood. In the present study, we focus on the RTK ErbB3 and elucidate the mechanisms regulating its trafficking. We show that heregulin-stimulation induces trafficking of phosphorylated ErbB3 from the plasma membrane to the nucleus via a clathrin-independent mechanism. Nuclear import of ErbB3 occurs via importin ß1, which drives the receptor through the nuclear pore complex. In the nucleus, ErbB3 interacts with transcription complexes, and thereby has a role in transcriptional regulation. Our results also demonstrate that ErbB3 nuclear localization is transient as it is exported out of the nucleus by the nuclear receptor protein crm-1. Analysis of normal, regenerating tissues, and tumors showed that ErbB3 nuclear translocation is a common event in proliferating tissues.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Clathrin
/
Receptor, ErbB-3
/
Nuclear Pore
/
Cell Proliferation
/
Endocytosis
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2016
Type:
Article