EGF receptor phosphorylation is affected by ionizing radiation.
Eukaryotic cells respond to ionizing radiation with cell cycle arrest, activation of DNA repair mechanisms, and lethality. However, little is known about the molecular mechanisms that constitute these responses. Here we report that ionizing radiation enhances epidermal growth factor (EGF) receptor tyrosine phosphorylation in intact cells as well as in isolated membranes of A431 cells. Phosphoamino acid analysis revealed that ionizing radiation preferentially enhances tyrosine phosphorylation, while EGF enhances the phosphorylation of all three phosphoamino acids (serine, threonine and tyrosine) of the EGF receptor. In addition, radiation reduces the turnover rate of the EGF receptor, while EGF increases the rate of the receptor turnover and down-regulation. Moreover, the confined radiation-induced phosphorylation of tyrosine residues is inhibited by genistein, indicating that this phosphorylation of EGF receptor is due to protein tyrosine kinase activation. These studies provide novel insights into the capacity of radiation to modulate EGF receptor phosphorylation and function. The radiation-induced elevation in the EGF receptor tyrosine phosphorylation and the receptor's slower rate of turnover are discussed in terms of their possible role in cell growth and apoptosis modulation.
Goldkorn
T
T
Department of Medicine, University of California, Davis School of Medicine, 95616, USA.
Balaban
N
N
Shannon
M
M
Matsukuma
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002588:Cesium Radioisotopes; D004307:Dose-Response Relationship, Radiation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000032:analysis; D010769:Phosphothreonine / Q000032:analysis; D019000:Phosphotyrosine / Q000032:analysis
D002588:Cesium Radioisotopes; D010710:Phosphates; D010769:Phosphothreonine; D010768:Phosphoserine; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate; D008715:Methionine; D066246:ErbB Receptors