Kinase Subfamily MEKK2

From WikiKinome
Jump to: navigation, search

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 an N-terminal PB1 domain, a middle linker region, and a kinase domain at the C terminus. PB1 domains are also found in MEK5 and these domains 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

  1. Nakamura K and Johnson GL. Noncanonical function of MEKK2 and MEK5 PB1 domains for coordinated extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase signaling. Mol Cell Biol. 2007 Jun;27(12):4566-77. DOI:10.1128/MCB.00125-07 | PubMed ID:17452462 | HubMed [Nakamura]