Metabolic effects induced by epidermal growth factor (EGF) in cells expressing EGF receptor mutants.
The epidermal growth factor (EGF) receptor tyrosine kinase activity is required for both the earliest EGF-stimulated post-binding events (enhancement of inositol phosphate formation and Ca2+ influx, activation of Na+/H+ exchange), and the ultimate EGF-induced mitogenic response. To assess the role of EGF receptor kinase in EGF-induced metabolic effects (2-deoxyglucose and 2-aminoisobutyric acid uptake), we used NIH3T3 cells (clone 2.2), which do not possess endogenous EGF receptors and which were transfected with cDNA constructs encoding either wild type or kinase-deficient human EGF receptor (HER). In addition, we tested the importance of three HER autophosphorylation sites (Tyr-1068, Tyr-1148, and Tyr-1173) in transduction of EGF-stimulated 2-deoxyglucose uptake. Taking our data together, we conclude the following: (i) HER tyrosine kinase activity is required to elicit EGF stimulation of both 2-deoxyglucose and 2-aminoisobutyric acid uptake; (ii) mutations on individual HER autophosphorylation sites, Tyr-1068, Tyr-1148, and Tyr-1173 do not impair EGF-stimulated 2-deoxyglucose uptake.
Scimeca
J C
JC
Institut National de la Santé et de la Recherche Médicale U145, Faculté de Médecine, Nice, France.
Ballotti
R
R
Alengrin
F
F
Honegger
A M
AM
Ullrich
A
A
Schlessinger
J
J
Obberghen
E V
EV
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D004252:DNA Mutational Analysis; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D013329:Structure-Activity Relationship; D014162:Transfection; D014443:Tyrosine
D000621:Aminoisobutyric Acids; D003837:Deoxy Sugars; C100049:2-aminoisobutyric acid; D014443:Tyrosine; D004815:Epidermal Growth Factor; D003847:Deoxyglucose; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases