Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor

摘要: Epidermal growth factor (EGF) induces cell proliferation in a variety of types by binding to prototype transmembrane tyrosine kinase receptor1,2. Ligation this receptor EGF activates Erk1 and Erk2, members the mitogen-activated protein (MAP) family, through Ras-dependent signal transduction pathway3,4,5. Despite our detailed understanding these events, exact mechanism which causes cells proliferate is unclear. Big MAP (Bmk1), also known as Erk5, member family that activated response oxidative stress, hyperosmolarity treatment with serum6,7. Here we show potent activator Bmk1. In contrast Erk1/2, EGF-mediated activation Bmk1 occurs independently Ras requires MAP-kinase Mek5. Expression dominant-negative form blocks EGF-induced prevents from entering S phase cycle. These results demonstrate part distinct signalling pathway required for progression