Overview:

MEK1 (MAP Kinase Kinase, MKK) is a member of the dual specificity protein kinase family. MEK1 lies upstream of MAPK/ERK and stimulates the enzymatic activity of MAPK/ERK upon a wide variety of extra- and intracellular signals. As an essential component of the MAPK/ERK signal transduction pathway, MEK1 is involved in many cellular processes such as proliferation, differentiation, transcriptional regulation and development (1). This pathway plays a key role in synaptic plasticity in the brain (2). Constitutive activation of MEK1 results in cellular transformation. Thus, MEK 1 represents a likely target for pharmacological intervention in proliferative diseases such as cancer (3). Ser222 is essential for the kinase activity of MEK1 (4).

References:

1. Seger, R. et al: The MAPK signaling cascade. FASEB J. 1995 Jun;9(9):726-35.

2. Adams, J P. et al: Molecular psychology: Roles for the ERK MAP kinase cascade in memory. Annu Rev Pharmacol Toxicol 2002 42:135-163.

3. Sebolt-Leopold, J S. et al: Blockade of the MAP Kinase Pathway Suppresses growth of colon tumors in vivo. Nature Med. 1999 5: 810-816.

4. Pagès G. et al: Co nstitutive mutant and putative regulatory serine phosphorylation site of mammalian MAP kinase kinase (MEK1). EMBO J. 1994 Jul 1;13(13):3003-10.