UV-Radiation-Induced Internalization of the Epidermal Growth Factor Receptor Requires Distinct Serine and Tyrosine Residues in the Cytoplasmic Carboxy-Terminal Domain

2004 ◽  
Vol 161 (6) ◽  
pp. 685-691 ◽  
Author(s):  
Morten P. Oksvold ◽  
Christine B. F. Thien ◽  
Jannicke Widerberg ◽  
Andrew Chantry ◽  
Henrik S. Huitfeldt ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Uv Radiation ◽  
Growth Factor Receptor ◽  
Tyrosine Residues ◽  
Carboxy Terminal Domain ◽  
Radiation Induced ◽  
Epidermal Growth ◽  
Carboxy Terminal

The carboxy-terminal domains of erbB-2 and epidermal growth factor receptor exert different regulatory effects on intrinsic receptor tyrosine kinase function and transforming activity

1990 ◽  
Vol 10 (6) ◽  
pp. 2749-2756
Author(s):  
P P Di Fiore ◽  
O Segatto ◽  
F Lonardo ◽  
F Fazioli ◽  
J H Pierce ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Kinase Activity ◽  
Growth Factor Receptor ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Epidermal Growth ◽  
Regulatory Effects ◽  
Carboxy Terminal

The erbB-2 gene product, gp185erbB-2, displays a potent transforming effect when overexpressed in NIH 3T3 cells. In addition, it possesses constitutively high levels of tyrosine kinase activity in the absence of exogenously added ligand. In this study, we demonstrate that its carboxy-terminal domain exerts an enhancing effect on erbB-2 kinase and transforming activities. A premature termination mutant of the erbB-2 protein, lacking the entire carboxy-terminal domain (erbB-2 delta 1050), showed a 40-fold reduction in transforming ability and a lowered in vivo kinase activity for intracellular substrates. When the carboxy-terminal domain of erbB-2 was substituted for its analogous region in the epidermal growth factor receptor (EGFR) (EGFR/erbB-2COOH chimera), it conferred erbB-2-like properties to the EGFR, including transforming ability in the absence of epidermal growth factor, elevated constitutive autokinase activity in vivo and in vitro, and constitutive ability to phosphorylate phospholipase C-gamma. Conversely, a chimeric erbB-2 molecule bearing an EGFR carboxy-terminal domain (erbB-2/EGFRCOOH chimera) showed reduced transforming and kinase activity with respect to the wild-type erbB-2 and was only slightly more efficient than the erbB-2 delta 1050 mutant. Thus, we conclude that the carboxy-terminal domains of erbB-2 and EGFR exert different regulatory effects on receptor kinase function and biological activity. The up regulation of gp185erbB-2 enzymatic activity exerted by its carboxy-terminal domain can explain, at least in part, its constitutive level of kinase activity.

scholarly journals Expression of Epidermal Growth Factor Receptor in Plutonium-239-induced Lung Neoplasms in Dogs

1992 ◽  
Vol 29 (1) ◽  
pp. 46-52 ◽  
Author(s):  
N. A. Gillett ◽  
B. L. Stegelmeier ◽  
G. Kelly ◽  
P. J. Haley ◽  
F. F. Hahn
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Lung Tumors ◽  
Lung Carcinogenesis ◽  
Preneoplastic Lesions ◽  
Radiation Induced ◽  
Epidermal Growth

The expression of epidermal growth factor receptor (EGF-R) was examined in canine lung tumors and in proliferative epithelial foci induced by plutonium-239 to determine if EGF-R was associated with specific neoplastic phenotypes or putative preneoplastic lesions. Seventeen (47%) of 36 canine lung tumors expressed EGF-R. Of these 17 tumors, three tumors hybridized with an erb-B RNA probe, which identified activated cell oncogenes. The expression of EGF-R was not correlated with tumor etiology, e.g., spontaneous versus radiation induced, but did correlate with specific histologic phenotypes. Nineteen (15%) of 127 proliferative epithelial foci in the canine lungs also expressed EGF-R. The phenotypic specificity demonstrated for EGF-R in canine lung tumors parallels that previously shown in human lung tumors. This finding, in addition to the identification of EGF-R in nonneoplastic proliferative lung lesions, indicates that radiation-induced lung tumors in the dog may be a useful animal model to investigate the role of EGF-R in lung carcinogenesis.

scholarly journals The carboxy-terminal domains of erbB-2 and epidermal growth factor receptor exert different regulatory effects on intrinsic receptor tyrosine kinase function and transforming activity.

1990 ◽  
Vol 10 (6) ◽  
pp. 2749-2756 ◽  
Author(s):  
P P Di Fiore ◽  
O Segatto ◽  
F Lonardo ◽  
F Fazioli ◽  
J H Pierce ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Kinase Activity ◽  
Growth Factor Receptor ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Epidermal Growth ◽  
Regulatory Effects ◽  
Carboxy Terminal

The erbB-2 gene product, gp185erbB-2, displays a potent transforming effect when overexpressed in NIH 3T3 cells. In addition, it possesses constitutively high levels of tyrosine kinase activity in the absence of exogenously added ligand. In this study, we demonstrate that its carboxy-terminal domain exerts an enhancing effect on erbB-2 kinase and transforming activities. A premature termination mutant of the erbB-2 protein, lacking the entire carboxy-terminal domain (erbB-2 delta 1050), showed a 40-fold reduction in transforming ability and a lowered in vivo kinase activity for intracellular substrates. When the carboxy-terminal domain of erbB-2 was substituted for its analogous region in the epidermal growth factor receptor (EGFR) (EGFR/erbB-2COOH chimera), it conferred erbB-2-like properties to the EGFR, including transforming ability in the absence of epidermal growth factor, elevated constitutive autokinase activity in vivo and in vitro, and constitutive ability to phosphorylate phospholipase C-gamma. Conversely, a chimeric erbB-2 molecule bearing an EGFR carboxy-terminal domain (erbB-2/EGFRCOOH chimera) showed reduced transforming and kinase activity with respect to the wild-type erbB-2 and was only slightly more efficient than the erbB-2 delta 1050 mutant. Thus, we conclude that the carboxy-terminal domains of erbB-2 and EGFR exert different regulatory effects on receptor kinase function and biological activity. The up regulation of gp185erbB-2 enzymatic activity exerted by its carboxy-terminal domain can explain, at least in part, its constitutive level of kinase activity.

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