title: 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.
authors.affiliation: Department of Pharmaceutical Biochemistry, Poznań University of Medical Sciences, Święcickiego Str. 4, 60-781 Poznań, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Cichocki
authors.forename: Mateusz
authors.initials: M
authors.lastname: Szamałek
authors.forename: Miłosz
authors.initials: M
authors.lastname: Dałek
authors.forename: Wanda
authors.initials: W
authors.lastname: Baer-Dubowska
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D020134:Catalytic Domain; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D018808:Transcription Factor AP-1; D014443:Tyrosine; D066246:ErbB Receptors; D048031:JNK Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate