Abstract: A functional mammalian growth factor receptor/yeast histidine kinase chimera in Saccharomyces cerevisiae. In a preferred embodiment, the extracellular domain of the human epidermal growth factor receptor has been fused to the intracellular kinase domain of the SLN1 gene. The SLN1 gene encodes the plasma membrane sensor kinase of the yeast high osmolarity/glycerol response MAP kinase pathway. The chimeric protein is almost completely nonfunctional because the EGFR ECD is not capable of dimerization in the absence of ligand. In the presence of ligand, however, the chimeric kinase is activated and phosphorylation through the pathway is quantitatively repressed. This measure of pathway activity can be utilized to identify agonists and antagonists of the EGFR and other tyrosine kinase growth factor receptors in yeast cells.