Abstract: The present invention relates to a method of screening for constitutively active mutants of a desired eukaryotic MAPK pathway member of a MAPK pathway member, comprising the steps of (a) providing a mutant yeast strain devoid of an upstream kinase; (b) providing a DNA library of different mutants of a mutagenized gene coding for the desired MAPK pathway member; (c) introducing said library into said yeast strain under conditions suitable for activation of the yeast MAPK pathway; (d) detecting an end-point indication for activation of the yeast pathway; and (e) optionally isolating said constitutively activated mutant from selected rescued clones. The invention further relates to isolated constitutively active mutants of the MAPK pathway member, and their various uses particularly, in a method of screening for substances which are inhibitors of a MAPK pathway, and in drug design.