The human papillomavirus type 16 E5 protein modulates ERK1/2 and p38 MAP kinase activation by an EGFR-independent process in stressed human keratinocytes.
The human papillomavirus type 16 E5 gene product has been shown to upregulate the activation of MAP kinases ERK1/2 and cellular proliferation promoted by EGF in a ligand-dependent process. We now report the growth factor-independent modulation of MAP kinases by HPV 16 E5 in human keratinocytes. After treatment with 600 mM sorbitol or low concentrations of anisomycin, E5-expressing cells upregulate the activation of ERK1/2. In addition, E5 enhances p38 activation after anisomycin but not after sorbitol treatment, but it has no effect on MAP kinases activation after shocking the cells with 300 mM sodium chloride. The E5-mediated, sorbitol-dependent increase in ERK1/2 activation is EGF-independent and is only partially inhibited by tyrphostin AG1478, which is known to inhibit specifically EGF receptor activation.
Crusius
K
K
Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Rodriguez
I
I
Alonso
A
A
D000841:Anisomycin / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation; D006358:Hot Temperature; D006801:Humans; D015151:Immunoblotting; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae; D012965:Sodium Chloride / Q000494:pharmacology; D013012:Sorbitol / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases; D000086082:Viroporin Proteins
D000841:Anisomycin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009856:Oncogene Proteins, Viral; D012965:Sodium Chloride; D013012:Sorbitol; D048051:p38 Mitogen-Activated Protein Kinases; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins