MAP2K7

[6] MKK7 is involved in signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses.

[8] MKK7 has three conserved D-motifs (MAPK-recruiting short linear motifs) on its intrinsically disordered N-terminus.

[8] The D-motifs found in MKK7 are highly specific for JNKs, but have a relatively low binding affinity.

[10] The DVD region is a stable, mostly helical fold of roughly 20 amino acids, that adds onto the back side of the catalytic core of the MAP2K kinase domains.

[13] This domain extension is both required for the specific binding to, and activation of MKK7 by respective upstream MAPKKKs.

[9] MKK7 play an important part in the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway.

The MKKKs relate to MKK7 through its DVD site at the C-terminus and phosphorylate MKK7 at serine and threonine residues.

In addition to their "normal" cargoes (C-termini of transmembrane proteins), they also transport MAP2K and MAP3K enzymes, namely MKK7, DLK and MLK3.

[18] Since the cargo-linkage mechanism of this complex is believed to be phosphporylation-dependent, phosphorylation by JNK kinase can release its own upstream activators from the scaffold, thus driving a strong local positive feedback loop.

[16] MKK7 has also been suggested to function as a putative Metastase Suppressor Gene (MSG) by possibly promoting tumor dormancy at the metastatic site.

[33] In small mammals, stress like pressure overload can cause cardiac hypertrophy and failure if MKK7 is knocked out.

[34] Conditional deletion of Map2k7 in neural stem cells and postmitotic neurons identified a role for MKK7 in axonal elongation.

The architecture of MKK7: Box-model illustration of the structure of MKK7. [ 9 ]
Scaffold protein: A tradiational model showing how a scaffold protein is envisioned to bind a MAPKKK, MAPKK and a MAPK in a multienzyme complex. [ 16 ] Note that this model is outdated for JIP1, as it does not assemble an on-scaffold kinase cascade, but provides a selective release of MKK7 and DLK in specific compartments instead [ 18 ]