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 activ ators 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 ex ert its effect by preventing the guanine nucleotide exchange factor mS os from converting Pas to its active GTP-bound state. Exposure to arse nite may be a simple way of assessing whether Pas plays an essential r ole in mediating activation of the MAP kinase cascade by extracellular signals.