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1 June 2004 UV-Radiation-Induced Internalization of the Epidermal Growth Factor Receptor Requires Distinct Serine and Tyrosine Residues in the Cytoplasmic Carboxy-Terminal Domain
Morten P. Oksvold, Christine B. F. Thien, Jannicke Widerberg, Andrew Chantry, Henrik S. Huitfeldt, Wallace Y. Langdon
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Abstract

Oksvold, M. P., Thien, C. B. F, Widerberg, J., Chantry, A., Huitfeldt, H. S. and Langdon, W. Y. UV-Radiation-Induced Internalization of the Epidermal Growth Factor Receptor Requires Distinct Serine and Tyrosine Residues in the Cytoplasmic Carboxy-Terminal Domain. Radiat. Res. 161, 685–691 (2004).

The mechanism of UV-radiation-induced EGF receptor (EGFR) internalization remains to be established. In the present study, we found UV-radiation-mediated internalization of the EGFR to be dependent on the cytoplasmic carboxy-terminal region. UV radiation was unable to induce internalization of EGFR carboxy-terminal truncation mutants where all or four of the five major autophosphorylation sites were missing (963- and 1028-EGFR, respectively). Mutational removal of serine residues 1046, 1047, 1057 and 1142 within the carboxy-terminal receptor region was also sufficient to abolish UV-radiation-induced internalization of the EGFR. Furthermore, the UV-radiation-induced internalization was abrogated for an EGFR mutated in tyrosine 1045 (Y1045F), the major c-Cbl binding site. However, UV radiation did not induce phosphorylation at tyrosine 1045, in contrast to the prominent phosphorylation induced by EGF. Our results suggest a mechanism for UV-radiation-induced internalization of EGFR involving a conformational change that is dependent on structural elements formed by specific serine and tyrosine residues in the carboxy-terminal domain.

Morten P. Oksvold, Christine B. F. Thien, Jannicke Widerberg, Andrew Chantry, Henrik S. Huitfeldt, and Wallace Y. Langdon "UV-Radiation-Induced Internalization of the Epidermal Growth Factor Receptor Requires Distinct Serine and Tyrosine Residues in the Cytoplasmic Carboxy-Terminal Domain," Radiation Research 161(6), 685-691, (1 June 2004). https://doi.org/10.1667/RR3185
Received: 29 September 2003; Accepted: 1 January 2004; Published: 1 June 2004
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