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Compartmentalization of the Mitogen-Activated Protein Kinase (MAPK) in Hepatic Endosomes: Association with the Internalized Epidermal Growth Factor (EGF) Receptor
Affiliation:1. Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA;2. Department of Psychiatry and Behavioral Neurosciences, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA;1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UPMC Hillman Cancer Center and the Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA;2. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA;1. Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, QC, Canada;2. Experimental Medicine, McGill University, Montreal, QC, Canada;3. Experimental Surgery, McGill University, Montreal, QC, Canada;4. Division of Gynecologic Oncology, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, QC, Canada
Abstract:A pool of MAPK was found in hepatic plasma membrane (PM) and endosomes (ENs). After injection of a single dose of EGF (10 μg/100 g body weight), MAPK was detected in EGF receptor (EGFR) immunoprecipitates prepared from ENs. MAPK was detected in a time-dependent manner in EGFR immunoprecipitates that was coincident with the progressive concentration of the EGFR. The EGFR-associated MAPK was also detected by using an anti-phospho-MAPK suggesting that it was active. MAPK was present in wheat-germ agglutinin (WGA) eluates prepared from ENs and was maximally tyrosine-phosphorylated at the time peak of EGFR internalization. MAPK therefore is compartmentalized in PM and ENs of rat liver. A fraction of the endosomal MAPK was found to be associated with the internalized EGFR complexes, suggesting that it plays a role in the control of the EGFR activity at this locus.
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