Menadione (vitamin K3) enhances the mitogenic signal of epidermal growth factor via extracellular signal-regulated kinases.
The effects of vitamin K3 (VK3) on DNA synthesis, cell proliferation and mitogen-activated protein kinase pathway were investigated in G0-arrested NIH 3T3 fibroblasts. VK3 (5 microM) alone stimulates DNA synthesis by 40% and moderately increases the mitogenic effects of EGF, which is preceded by a rapid phosphorylation of the extracellular signal-regulated kinases (ERKs). At 20 microM, VK3 had an antiproliferative effect. VK3 alone (5 and 50 microM) or in concert with EGF increases the activity of ERK2 (by 2.5 and 5 fold, respectively). Our studies demonstrate that the activation of ERKs by VK3 alone, or VK3 plus EGF can promote either stimulatory or inhibitory effects on the mitogenic signal.
Markovits
J
J
Division of Cancer Research, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Sun
T P
TP
Juan
C C
CC
Ju
G C
GC
Wu
F Y
FY
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D054638:Dual Specificity Phosphatase 1; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000502:physiology; D017874:Immediate-Early Proteins / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D008934:Mitogens / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014812:Vitamin K / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D008934:Mitogens; D010455:Peptides; D014812:Vitamin K; D004815:Epidermal Growth Factor; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases