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Correlation between EGFR Y1068 tyrosine phosphorylation and AP-1 activation by tumor promoter 12-O-tetradecanoylphorbol-13-acetate in mouse skin.

Abstract
The mouse skin carcinogenesis is unique model for our understating of molecular events leading to tumor development. The tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) activates a variety of signaling pathways, including MAPK/AP-1. In this study, we examined the time course of EGFR phosphorylation and AP-1 activation in mouse epidermis after topical application of a single 10 nmol dose of TPA. Remarkable differences in the phosphorylation kinetics of EGFR tyrosine residues were observed. While the maximal level of Y1068 tyrosine phosphorylation occurred 4h after TPA treatment, the Y1173 residue phosphorylation was initially down-regulated, and reached the highest level after 24 h. Phosphorylation of Y1068 tyrosine was correlated with AP-1 activation and c-Jun N-terminal kinase (JNK) activity. These results indicate that the stimulation of AP-1 in mouse epidermis by TPA may be the effect of EGFR activation, but not all tyrosine residues forming its catalytic center are equally involved in this process.
AuthorsMichał Cichocki, Mateusz Szamałek, Miłosz Dałek, Wanda Baer-Dubowska
JournalEnvironmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 33 Issue 1 Pg. 92-7 (Jan 2012) ISSN: 1872-7077 [Electronic] Netherlands
PMID22196048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Carcinogens
  • Transcription Factor AP-1
  • Tyrosine
  • ErbB Receptors
  • JNK Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate
Topics
  • Animals
  • Carcinogens (pharmacology)
  • Catalytic Domain
  • Enzyme Activation (drug effects)
  • ErbB Receptors (chemistry, genetics, metabolism)
  • Female
  • JNK Mitogen-Activated Protein Kinases (metabolism)
  • Mice
  • Phosphorylation
  • Signal Transduction (drug effects)
  • Skin (drug effects, metabolism)
  • Tetradecanoylphorbol Acetate (pharmacology)
  • Transcription Factor AP-1 (metabolism)
  • Tyrosine (metabolism)

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