Enhancement of EGF- and PMA-mediated MAP kinase activation in cells expressing the human papillomavirus type 16 E5 protein.
In this report we demonstrate that cells expressing the human papillomavirus type 16 E5 open reading frame (HPV16-E5) show a greatly enhanced transcription of the immediate early genes after EGF or PMA treatment compared to control cells. This enhancement is due to amplification of the signal transduction pathways in response to growth factors or phorbol esters. Upon short-time EGF treatment of the E5-expressing cells we observed an increase in the activation of EGF receptors, resulting in a stronger activation of MAP kinases ERK1/2 compared to control-transfected cells. We also observed that in E5-expressing cells, treatment with PMA results in an increase in membrane-associated PKC activity, and a superactivation of the ERK1/2 MAP kinases. This superactivation is PKC-dependent, since pretreatment of the cells with the PKC inhibitor Ro 31-8220 inhibits MAP kinase activation and early gene transcription almost completely. Furthermore, treatment with genistein strongly reduces the PMA-mediated superactivation of ERK1/2 kinases, demonstrating a PKC-mediated, tyrosine kinase-dependent pathway in the superinduction of MAP kinase activation. Thus, HPV16-E5 effects superactivation of MAP kinases over at least two different pathways, a PKC-mediated, and another, receptor tyrosine-kinase mediated, PKC-independent one.
Crusius
K
K
Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Auvinen
E
E
Alonso
A
A
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis*; D016366:Open Reading Frames; D027383:Papillomaviridae / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection; D000086082:Viroporin Proteins
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D007211:Indoles; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009856:Oncogene Proteins, Viral; D011493:Protein Kinase C; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins; C064758:Ro 31-8220