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Role of Protein Kinase C (PKC) in Epidermal Growth Factor Receptor (EGFR) Trafficking in Human Embryonic Kidney 293 (HEK293) Cells
Author(s) -
Baldys Aleksander,
Raymond John
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a115
Subject(s) - endosome , microbiology and biotechnology , receptor , endocytosis , transactivation , hek 293 cells , protein kinase c , epidermal growth factor , epidermal growth factor receptor , clathrin , chemistry , signal transducing adaptor protein , biology , signal transduction , biochemistry , transcription factor , gene
Activated EGF receptors are rapidly removed from plasma membrane through clathrin‐dependent endocytosis and subsequently degraded in lysosomes or recycled back to cell surface. Using confocal microscopy we examined the fate of EGF receptors after activation by its natural ligands, or transactivation by G protein‐coupled receptors (5‐HT2A). Our results demonstrate that some ligands do not cause delivery of activated EGFR to lysosomes or receptor degradation, but rather to a transferrin‐ and Rab11‐positive recycling endosomes. Most importantly, we provide evidence that PKC plays a critical role in the formation of these endosomes. Interestingly, we also report that 5‐HT2A receptors transactivate EGFR in a PKC‐dependent manner, and that both receptors are trafficked simultaneously to a similar, perinuclear compartment. Taken together, it appears that PKC acts as a molecular switch that directs EGF receptors to either lysosomal degradation or to their default recycling pathway. Supported by NIH DK052448 and GM063909; VA SEG and REAP awards