Function
Mitogen-activated protein kinase kinase or dual specificity mitogen-activated protein kinase kinase (MAP2K; MEK1 or MEK2)) are serine/threonine kinases which regulate various cellular activities in response to extracellular stimuli by mitogens, heat shock and more. MAP2K is part of the MAPK cascade which consists also of MAPK and MAP3K which are activated by phosphorylation. The PB1 domain at the N-terminal of MAP2K is involved in the heterodimerization and is required for the formation of macromolecular signalling complexes which ensure specificity and fidelity during cellular signalling[1]. MAP2K activates MAPK[2],[3].
- MAP2K1 slows down sister chromatid association in meiosis.
- MAP2K2 phosphorylates MAPK1 and MAPK2.
- MAP2K3 phosphorylates MAPK14.
- MAP2K4 phosphorylates MAPK8, MAPK9 and MAPK14.
- MAP2K5 phosphorylates MAPK7.
- MAP2K6 phosphorylates p38-MAPKs in response to stress.
- MAP2K7 phosphorylates MAPK8 and MAPK9.
Relevance
MAP2K is activated in melanoma and its inhibitors are tested as therapeutical agents[4].
Disease
MAP2K4 mutations are seen in many types of cancer and particularly in breast cancer[5].
Structural highlights
The biological assembly of Human MAP2K1 is . MAP2K inhibitors interact with the active site ATP[6].
3D Structures of Mitogen-activated protein kinase kinase