MP1 - A MEK BINDING PARTNER THAT ENHANCES ENZYMATIC ACTIVATION OF THEMAP KINASE CASCADE

Signal transduction is controlled both by regulation of enzyme activat ion and by organization of enzymatic complexes with nonenzymatic adapt ers, scaffolds, and anchor proteins. The extracellular signal-regulate d kinase (ERK) cascade is one of several evolutionarily conserved mito gen-activated protein (MAP) kinase cascades important in the regulatio n of growth, apoptosis, and differentiation. A two-hybrid screen was c onducted to identify nonenzymatic components of this signaling cascade that might be important in regulating its activity. A protein called MP1 (MEK Partner 1) was identified that bound specifically to MEK1 and ERK1 and facilitated their activation. When overexpressed in cultured cells, MP1 enhanced activation of ERK1 and activation of a reporter d riven by the transcription factor Elk-1. Expression of MP1 in cells in creased binding of ERK1 to MEK1. MP1 apparently functions as an adapte r to enhance the efficiency of the MAP kinase cascade.