title: Activation of ErbB2 by 2-methyl-1,4-naphthoquinone (menadione) in human keratinocytes: role of EGFR and protein tyrosine phosphatases.
abstract: Activation of ErbB receptor tyrosine kinases triggers multiple signaling pathways that regulate cellular proliferation and survival. We here demonstrate that ErbB2 is activated via the epidermal growth factor receptor (EGFR) upon exposure of cultured human keratinocytes to 2-methyl-1,4-naphthoquinone (menadione). Both ErbB2 and EGFR are shown to be regulated by protein tyrosine phosphatases that are inhibited by menadione, giving rise to the hypothesis that phosphatase inhibition by menadione may result in a net activation of EGFR and an enhanced ErbB2 phosphorylation. Isolated PTP-1B, a protein tyrosine phosphatase known to be associated with ErbB receptors, is demonstrated to be inhibited by menadione.
authors.affiliation: Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, Geb. 22.03; D-40225 Düsseldorf, Germany.
authors.forename: Juliane I
authors.initials: JI
authors.lastname: Beier
authors.forename: Claudia
authors.initials: C
authors.lastname: von Montfort
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
authors.forename: Lars-Oliver
authors.initials: LO
authors.lastname: Klotz
mesh_terms: D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D024483:Vitamin K 3 / Q000494:pharmacology*
chemical_list: D066246:ErbB Receptors; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D018719:Erb-b2 Receptor Tyrosine Kinases; D024483:Vitamin K 3; C516607:PTPN1 protein, human