MAP2K7

MAP2K7 is also known as: • MKK7 • JNK-activated kinase 2 • MAPK/ERK kinase 7 (MEK7) • Stress-activated protein kinase kinase 4 (SAPK kinase 4, SAPKK4) • c-Jun N-terminal kinase kinase 2 (JNK kinase 2, JNKK2) • Stress-activated / extracellular signal-regulated protein kinase kinase 2 (SEK2) == Isoforms ==

The murine MKK7 protein is encoded by 14 exons which can be alternatively spliced to yield a group of protein kinases. This results in six isoforms with three possible N-termini (α, β, and γ isoforms) and two possible C-termini (1 and 2 isoforms). The molecular mass of the isoforms spans from 38 to 52 kDa, with between 345 and 467 amino acids. The physiological relevance of the different MKK7 isoforms is still unclear. Evidence shows that the MKK7α, which lacks an NH2-terminal extension, shows a lower basal activity in binding JNK compared to the MKKβ and γ isoforms. The increased basal activity in the β and γ isoforms can be due to the three D-motifs present in the N-terminus of these isoforms. == Structure and function ==

upstream. These special MAPKK:MAPKKK kinase-domain/kinase-domain interactions facilitate the phosphorylation of MKK7. In addition to the activation of MKK7, binding to the DVD region may also affect the MKK7 activation loop in such a way that the Ser and Thr of the S-K-A-K-T motif become accessible for phosphorylation. Kinase domain The MKK7 contains one kinase domain. The direct MKK7:MAPKKK interaction (using the DVD region), facilitates the phosphorylation of MKK7 by MAPKKKs on serine and threonine in a S-K-A-K-T motif in the catalytic domain (kinase domain). == Signaling and regulation ==

MKK7 play an important part in the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In collaboration with another mitogen-activated protein kinase kinase MKK4, MKK7 work as crucial transducers upstream of JNK signaling. Through joint efforts the two MKKs phosphorylate different JNK isoforms. As a result, MKK7 has a great impact on numerous physiological processes such as proliferation and differentiation, as well as pathological processes such as apoptosis and tumorigenesis. MKK7 are activated as a result of cellular stresses. Scaffold proteins In addition to the direct interactions between JNK, MKK7 and other upstream protein kinases, various scaffold proteins function to ensure specificity between the components of the MAPK signaling cascade. Plenty of Src-homology-3 (POSH) has also been shown to be a partner of JIP1/2. == Interactions ==

MAP2K7 has been shown to interact with: • CNKSR1 • MAP3K1 • MAPK8 • MAPK8IP3 • MAPK8IP1 • GADD45B • MAP3K12 • MAP3K2 • DUSP19 == Biological relevance ==

MKK7 is involved in the development of epithelial tissues such as skin and lungs, and also the developing teeth, during early embryogenesis in mice. In small mammals, stress like pressure overload can cause cardiac hypertrophy and failure if MKK7 is knocked out. Conditional deletion of Map2k7 in neural stem cells and postmitotic neurons identified a role for MKK7 in axonal elongation. Neuron-specific deletion of Map2k7 showed a role for MKK7 in age-dependent motor dysfunction. Genetic variations in MAP2K7 have been associated with schizophrenia in humans. == References ==