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.
Department of Biochemistry, Medical Sciences Institute, The University of Dundee, UK.
Y N
YN
Doza
C A
CA
Hall-Jackson
P
P
Cohen
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