MAP KINASE KINASE FROM RABBIT SKELETAL-MUSCLE - A NOVEL DUAL SPECIFICITY ENZYME SHOWING HOMOLOGY TO YEAST PROTEIN-KINASES INVOLVED IN PHEROMONE-DEPENDENT SIGNAL TRANSDUCTION

MAP kinase kinase (MAPKK) was purified 30.000-fold to homogeneity from extracts of rabbit skeletal muscle and shown to be a monomeric protein of apparent molecular mass 44 kDa. MAPKK activated the 42 kDa isoform of MAP kinase by phosphorylation of Thr-183 and Tyr-185. and phosphorylated itself slowly on tyrosine, threonine and serine residues. establishing that it is a 'dual specificity' protein kinase. Peptide sequences from MAPKK were homologous to other protein serine/threonine kinases. especially to the subfamily that includes yeast protein kinases that lie upstream of yeast MAP kinase homologues in the pheromone-dependent mating pathways.