Investigating the Cellular BMK1/ERK5 Signaling Pathway

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is the most recently identified member of the mammalian mitogen-activated protein kinase (MAPK) family (1 ,2 ). Cellular activation of BMK1 is induced by a variety of stimuli including growth factors, oxidative stress, and hyperosmolar conditions (3 –7 ). These physiologic mediators activate cellular BMK1 through the direct and sequential activation of a signaling cascade comprising the kinases MEKK3, MEK5, and BMK1 (4 ,5 ,8 –10 ). We have shown that the activation of this signal transduction pathway is required for growth factor-mediated cell proliferation and cell-cycle progression (5 ,11 ).