Activation of ErbB2 by 2-methyl-1,4-naphthoquinone (menadione) in human keratinocytes: role of EGFR and protein tyrosine phosphatases.
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.
Beier
Juliane I
JI
Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, Geb. 22.03; D-40225 Düsseldorf, Germany.
von Montfort
Claudia
C
Sies
Helmut
H
Klotz
Lars-Oliver
LO
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*
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