|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Research Article |
1 Laboratory for Toxicopathology, Institute of Pathology, The National Hospital,
University of Oslo, N-0027 Oslo, Norway
2 Neurochemical Laboratory, Department Group of Basic Medical Sciences,
University of Oslo, N-0317 Oslo, Norway
3 Center for Cellular Stress Responses, University of Oslo, N-0027 Oslo,
Norway
* Author for correspondence (e-mail: m.p.oksvold{at}labmed.uio.no )
Accepted 1 November 2001
We have compared the activation and trafficking of epidermal growth factor receptor (EGFR) induced by UV light and EGF. Tyrosine phosphorylation of EGFR was not detected in UV-exposed cells by immunoblotting of whole cell lysates or EGFR immunoprecipitates with antibodies specific for each of the five activated autophosphorylation sites of EGFR. In addition, EGFR of UV-irradiated cells did not demonstrate increased 32P-incorporation. However, UV-exposed cells demonstrated a gel mobility shift of EGFR, which was not abolished by alkaline phosphatase treatment. UV-exposure did not induce dimerisation of EGFR. Furthermore, UV induced internalisation of EGFR without polyubiquitination or degradation. UV-exposed EGFR was transferred to early endosomes and arrested in transferrin-accessible endosomes close to the cell surface. Whereas inhibition of the EGFR tyrosine kinase effectively inhibited tyrosine phosphorylation and internalisation of EGF-activated EGFR, internalisation of UV-exposed EGFR was unaffected. UV induced neither relocalisation of Shc and Grb2 nor activation of Raf, but activation of MEK and MAPK was observed.
Our work indicates that UV induces internalisation of EGFR independent of its phosphorylation or receptor tyrosine kinase activation, and altered EGFR trafficking compared with ligand-activated receptor. In addition, MAPK activation by UV does not appear to be mediated by EGFR activation.
Key words: UV, EGF receptor, Receptor internalisation, Intracellular trafficking
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
![]() |
S. Adachi, M. Shimizu, Y. Shirakami, J. Yamauchi, H. Natsume, R. Matsushima-Nishiwaki, S. To, I.B. Weinstein, H. Moriwaki, and O. Kozawa (-)-Epigallocatechin gallate downregulates EGF receptor via phosphorylation at Ser1046/1047 by p38 MAPK in colon cancer cells Carcinogenesis, September 1, 2009; 30(9): 1544 - 1552. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. V. Abella and M. Park Breakdown of endocytosis in the oncogenic activation of receptor tyrosine kinases Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E973 - E984. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. B. El-Abaseri, S. Putta, and L. A. Hansen Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor Carcinogenesis, February 1, 2006; 27(2): 225 - 231. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Sun, J. Yuan, H. Liu, Z. Shi, K. Baker, K. Vuori, J. Wu, and G.-S. Feng Role of Gab1 in UV-Induced c-Jun NH2-Terminal Kinase Activation and Cell Apoptosis Mol. Cell. Biol., February 15, 2004; 24(4): 1531 - 1539. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y.-Y. He, J.-L. Huang, J. B. Gentry, and C. F. Chignell Epidermal Growth Factor Receptor Down-regulation Induced by UVA in Human Keratinocytes Does Not Require the Receptor Kinase Activity J. Biol. Chem., October 24, 2003; 278(43): 42457 - 42465. [Abstract] [Full Text] [PDF] |
||||