The Nuclear Accumulation of a Variant Epidermal Growth Factor Receptor (EGFR) Lacking the Transmembrane Domain Requires Coexpression of a Full-Length EGFR

摘要

Both the epidermal growth factor (EGF) and its receptor (EGFR) accumulate in the nucleoplasm during liver regeneration.This localization in a nonmembraneous compartment presents a challenge in that the standard form of EGFR is a transmembrane protein and suggests the existence of a variant, soluble form of EGFR.To investigate the localization of such a transmembrane-devoid form of EGFR.Ww placed this transmembrane-negative [TM(-)] EGFR construct and full-length wild-type (wt) EGFR express endogenous EGFR,were transfected with the TM(-) EGFR construct.The expression of these TM(-) EGFR,detected with a specific antibody against human EGFR using a confocal laser-scanning microscope,was predominantly found in the cytoplasm with no nuclear localization.After an overnight incubation with EGF the TM(-) EGFR accumulated in the nucleus.In mouse NR6 cells,which lack endogenous EGFR,transfected TM(-) EGFR were found in the cytoplasm,but incubation with EGF did not result in a nuclear accumulation of TM(-) EGFR.However,NR6 cells transfected with both TM(-) EGFR and wt EGFR showed nuclear accumulation after EGF treatment.These results suggest that both the wt EGFR and the TM(-) EGFR are required for nuclear accumulation of TM(-) EGFR and may implicate a model of homotypic recognition and translocaton of a splice variant of EGFR.