Kinase Subfamily MEKK2
Kinase Classification: Group STE: Family STE11: Subfamily MEKK2
MEKK2 is part of the ERK5-variant MAPK pathway: it phosphorylates MEK5, which in turn phosphorylates ERK5.
Evolution
MEKK2 is found only in holozoans, though it is secondarily lost from nematodes and insects. Vertebrates have two family members: MAP3K2 (MEKK2) and MAP3K3 (MEKK3).
Domain Structure
MEKK2 all have a C-terminal PB1 domain, a middle linger region, and a kinase domain at the C terminus. PB1 domains are also found in MEK5 and these mediate the heterodimerization of these two proteins [1].
Biological Function
MEKK2 is best known for activating the ERK5 and JNK MAPK pathways. Quiescent MEKK2 binds to the MEK5 MAP2K and ERK5 MAPK, enabling that MAPK cascade. Activated MEKK2 can then bind the MKK7 MAP2K, which leads to activation of the JNK MAPK.
References
- Kato Y, Zhao M, Morikawa A, Sugiyama T, Chakravortty D, Koide N, Yoshida T, Tapping RI, Yang Y, Yokochi T, and Lee JD. Big mitogen-activated kinase regulates multiple members of the MEF2 protein family. J Biol Chem. 2000 Jun 16;275(24):18534-40. DOI:10.1074/jbc.M001573200 |