Big mitogen-activated protein kinase (MAPK) 1 (BMK1), also known as ERK5, is a recently identified member of the mammalian MAPK family. Cellular stimulation of BMK1 is induced in response to growth factors, oxidative stress, and hyperosmolar conditions. Specific members of the myocyte enhancer factor 2 family of transcription factors that regulate growth factor-induced early gene expression have been identified as direct downstream targets of BMK1 activity. Recent studies have shown that growth factors of the epidermal growth factor family mediate the sequential activation of a kinase cascade consisting of MAPK kinase kinase 3, MAPK kinase 5, and BMK1. Most importantly, the activation of this signal transduction pathway has been shown to be required for growth factor-mediated cell proliferation and cell-cycle progression. Collectively, these studies establish BMK1 as an important regulator of growth factor-induced cellular responses.