Arsenite blocks growth factor induced activation of the MAP kinase cascade, upstream of Ras and downstream of Grb2-Sos.
Pretreatment of cells with 0.5 mM sodium arsenite (but not other activators of stress-activated MAP kinase cascades) prevents the activation of p21Ras and strongly suppresses the activation of c-Raf and the MAP kinase cascade by a variety of growth factors. Arsenite appears to exert its effect by preventing the guanine nucleotide exchange factor mSos from converting Ras to its active GTP-bound state. Exposure to arsenite may be a simple way of assessing whether Ras plays an essential role in mediating activation of the MAP kinase cascade by extracellular signals.
Doza
Y N
YN
Department of Biochemistry, Medical Sciences Institute, The University of Dundee, UK.
Hall-Jackson
C A
CA
Cohen
P
P
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051380:GRB2 Adaptor Protein; D020662:Guanine Nucleotide Exchange Factors; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D017670:Sodium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020663:ras Guanine Nucleotide Exchange Factors; D018631:ras Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018053:Arsenites; D004791:Enzyme Inhibitors; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D017670:Sodium Compounds; D020663:ras Guanine Nucleotide Exchange Factors; C017947:sodium arsenite; D004815:Epidermal Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins