MEK1/MAP2K1

MEK1, a MAP2K type protein kinase, is a member of the Ras MAPK pathway. This pathway modulates the activity of transcription factors, structural proteins and other protein kinases, leading to biological responses such as cell proliferation and differentiation. MEK1 contains a proline-rich segment that is recognized by the scaffold protein MEK binding partner-1 (MP1). MP1 associates with non-phosphorylated MEK1, forming a complex which associates with and phosphorylates MAP kinases ERK1 and 2. Additionally, MEK1 signaling is reported to have a strong negative effect on myogenic differentiation antigen (MYOD) activity via a mechanism involving the binding of MEK1 to the nuclear MYOD transcriptional complex. MEK1 is phosphorylated by several kinases, including Raf1, c-Mos and MEKK1. PAK1 also phosphorylates MEK1 resulting in enhancement of MEK’s interaction with Raf-1. Constitutive activation of MEK1 results in cellular transformation; thus, it is a likely target for pharmacologic intervention in proliferative disease. MEK inhibitors have been studied for clinical management of colon cancer and inhibition of viral replication in host cells. MEK1 is a substrate for the anthrax lethal factor (LF).

Image: MEK1 staining of Human Colon. Paraffin embedded.