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Literature summary for 2.7.12.2 extracted from

  • Wang, J.; Chen, L.; Ko, C.I.; Zhang, L.; Puga, A.; Xia, Y.
    Distinct signaling properties of mitogen-activated protein kinase kinases 4 (MKK4) and 7 (MKK7) in embryonic stem cell (ESC) differentiation (2012), J. Biol. Chem., 287, 2787-2797.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

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

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

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Mus musculus P47809
-
-
Mus musculus Q8CE90
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-

Source Tissue

Source Tissue Comment Organism Textmining
cardiomyocyte
-
Mus musculus
-
embryonic stem cell
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Mus musculus
-

Substrates and Products (Substrate)

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

Synonyms Comment Organism
mitogen-activated protein kinase kinase 4
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Mus musculus
mitogen-activated protein kinase kinase 7
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Mus musculus
MKK4
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Mus musculus
MKK7
-
Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
Mus musculus

General Information

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