The activation of signal transduction pathways by growth factors; hormones and neurotransmitters is mediated by the MAP kinases ERK 1 and ERK 2. ERK proteins are regulated by dual phosphorylation at specific tyrosine and threonine sites mapping within a characteristic Thr-Glu-Tyr motif. The protein kinase p56 KKIAMRE is distantly related to the MAP kinase group of proteins and is closely related to p42 KKIALRE. KKIAMRE is predominantly expressed in testis; kidney; brain and lung. KKIAMRE contains the conserved MAP kinase dual phosphorylation motif in the sequence Thr-Asp-Tyr and is activated by treatment of cells by EGF. However; unlike other MAP kinases; the EGF-stimulated kinase activity does not require phosphorylation of KKIAMRE and KKIALRE in the Thr-Asp-Tyr motif.