MAP2K2

MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2), also known as MEK2 (MAP/ERK Kinase 2), is a protein kinase enzyme encoded by the MAP2K2 gene in humans. It is a member of the MAP kinase kinase (MAPKK) or MEK family, which are dual-specificity kinases that phosphorylate both tyrosine and serine/threonine residues in their target proteins.

MAP2K2 functions as a critical component of the Ras/Raf/MEK/ERK signaling pathway, also known as the MAPK/ERK pathway. This pathway is involved in a wide range of cellular processes, including cell growth, proliferation, differentiation, movement, survival, and apoptosis. It mediates signal transduction from cell surface receptors to downstream effectors in the nucleus.

Specifically, MAP2K2 is activated by MAP3Ks (MAP kinase kinase kinases), such as RAF proteins (ARAF, BRAF, CRAF/RAF1). Once activated, MAP2K2 phosphorylates and activates the MAPKs ERK1 and ERK2 (extracellular signal-regulated kinases 1 and 2). Activated ERKs then translocate to the nucleus, where they phosphorylate and activate transcription factors, leading to changes in gene expression.

The MAP2K2 gene is located on chromosome 19p13.3. Mutations in MAP2K2 have been implicated in various developmental disorders, including cardiofaciocutaneous syndrome (CFCS).

MAP2K2 is a validated target for cancer therapy, as the MAPK/ERK pathway is frequently dysregulated in various cancers. Several MEK inhibitors have been developed and are used clinically to treat certain types of cancer, particularly melanoma harboring BRAF mutations. These inhibitors function by specifically binding to and inhibiting the activity of MAP2K1 and/or MAP2K2. While some MEK inhibitors are designed to inhibit both MEK1 and MEK2, there are differences in their binding affinity and selectivity.