MAP2K7

Description

The MAP2K7 (mitogen-activated protein kinase kinase 7) is a protein-coding gene located on chromosome 19.

Dual specificity mitogen-activated protein kinase kinase 7, also known as MAP kinase kinase 7 or MKK7, is an enzyme that in humans is encoded by the MAP2K7 gene. This protein is a member of the mitogen-activated protein kinase kinase family. The MKK7 protein exists as six different isoforms with three possible N-termini (α, β, and γ isoforms) and two possible C-termini (1 and 2 isoforms). MKK7 is involved in signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses. This kinase specifically activates MAPK8/JNK1 and MAPK9/JNK2, and this kinase itself is phosphorylated and activated by MAP kinase kinase kinases including MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK5, and MAP4K2/GCK. MKK7 is ubiquitously expressed in all tissue. However, it displays a higher level of expression in skeletal muscle. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found.

MAP2K7/MKK7 is a dual specificity protein kinase that plays a crucial role in the MAP kinase signal transduction pathway, particularly in the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. It is one of the only known kinases, along with MAP2K4/MKK4, that directly activates the JNKs (MAPK8/JNK1, MAPK9/JNK2, and MAPK10/JNK3) through phosphorylation. While both MAP2K4/MKK4 and MAP2K7/MKK7 activate JNKs, they exhibit distinct preferences for phosphorylation sites within the Thr-Pro-Tyr motif. MAP2K4/MKK4 favors phosphorylation of the Tyr residue, whereas MAP2K7/MKK7 prefers the Thr residue. Notably, monophosphorylation of JNKs at the Thr residue is sufficient to enhance JNK activity, highlighting the significance of MAP2K7/MKK7 in initiating JNK activation. The additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. MAP2K7/MKK7 is specifically involved in the JNK signal transduction pathway activated by pro-inflammatory cytokines. Furthermore, the MKK/JNK signaling pathway is implicated in mitochondrial death signaling, including the release of cytochrome c, ultimately leading to apoptosis. MAP2K7/MKK7 is also part of a non-canonical MAPK signaling pathway, involving the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1. This pathway enhances AP-1-mediated transcription of APP in response to APOE.

MAP2K7 is also known as JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7, SAPKK-4, SAPKK4.

Associated Diseases

WES Whole Exome Sequencing