Cloned (Comment) | Organism |
---|---|
gene MKK4, real-time RT-PCR expression analysis | Mus musculus |
gene MKK7, real-time RT-PCR expression analysis | Mus musculus |
Protein Variants | Comment | Organism |
---|---|---|
additional information | construction of MKK4 gene knockout mice, that show embryonic lethality | Mus musculus |
additional information | construction of MKK7 gene knockout mice, that show embryonic lethality | Mus musculus |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + JNK | Mus musculus | phosphorylation of JNK at the Thr residue located in the activation loop | ADP + phosphorylated JNK | - |
? | |
ATP + JNK | Mus musculus | phosphorylation of JNK at the Tyr residue located in the activation loop | ADP + phosphorylated JNK | - |
? | |
additional information | Mus musculus | MKK4 phosphorylates JNK on Tyr, while MKK7 phosphorylates Thr, and MKK4 and MKK7 together cause dual phosphorylation of JNK thus, optimal activation | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | P47809 | - |
- |
Mus musculus | Q8CE90 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
cardiomyocyte | - |
Mus musculus | - |
embryonic stem cell | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + JNK | phosphorylation of JNK at the Thr residue located in the activation loop | Mus musculus | ADP + phosphorylated JNK | - |
? | |
ATP + JNK | phosphorylation of JNK at the Tyr residue located in the activation loop | Mus musculus | ADP + phosphorylated JNK | - |
? | |
additional information | MKK4 phosphorylates JNK on Tyr, while MKK7 phosphorylates Thr, and MKK4 and MKK7 together cause dual phosphorylation of JNK thus, optimal activation | Mus musculus | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
mitogen-activated protein kinase kinase 4 | - |
Mus musculus |
mitogen-activated protein kinase kinase 7 | - |
Mus musculus |
MKK4 | - |
Mus musculus |
MKK7 | - |
Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Mus musculus |
General Information | Comment | Organism |
---|---|---|
malfunction | enzyme mutants show embryonic lethality. Mkk4 knockout embryonic stem cells exhibit diminished p-ATF2 and MEF2C expression, resulting in impaired MHC induction and defective cardiomyocyte differdifferentiation. Loss of MKK4 significantly blocks the induction of Mhca and Mhcb, but had no effect on expression of Mlc. Exogenous MKK4 expression partially restores the ability of Mkk4-/- embryonic stem cells to differentiate into cardiomyocytes. Mice lacking either MKK4 or MKK7 display an analogous embryonic lethal phenotype that may be attributed, at least in part, to insufficient JNK activation | Mus musculus |
malfunction | enzyme mutants show embryonic lethality. Mkk7 knockout embryonic stem cells show elevated phosphorylation of MKK4, p38, and ATF2, and increased MEF2C expression. The mutant cells show higher expression of MHC and MLC and enhanced formation of contractile cardiomyocytes. Mice lacking either MKK4 or MKK7 display an analogous embryonic lethal phenotype that may be attributed, at least in part, to insufficient JNK activation | Mus musculus |
metabolism | signal transduction pathways are integral components of the developmental regulatory network that guides progressive cell fate determination. Essential enzymes MKK4 and MKK7 are upstream kinases of the mitogen-activated protein kinases (MAPKs), responsible for channeling physiological and environmental signals to their cellular responses. In vitro, MKK4 and MKK7 are dispensable for in embryonic stem cell self-renewal and pluripotency maintenance, but they exhibit unique signaling and functional properties in differentiation. MKK4 and MKK7 complemented each other in activation of the JNK-c-Jun cascades and loss of both leads to senescence upon cell differentiation.On the other hand, MKK4 and MKK7 have opposite effects on activation of the p38 cascades during differentiation, MKK4 is required for cardiomyocyte differentiation, while MKK7 represses it | Mus musculus |
physiological function | MKK4 regulates Jun N-terminal kinase (JNK) and differentiating cell survival. And MKK4 is required for p38 activation and cardiomyocyte differentiation. Enzymes MKK4 and MKK7 have complementary and distinct roles in embryonic stem cell differentiation | Mus musculus |
physiological function | MKK7 regulates Jun N-terminal kinase (JNK) and differentiating cell survival. Enzymes MKK4 and MKK7 have complementary and distinct roles in embryonic stem cell differentiation. MKK7 reduces p38 activation | Mus musculus |