Mitogen-activated protein kinase kinase kinase 4 is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that in humans is encoded by the ''MAP3K4''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 (p38α) and JNK MAPKs are activated by

environmental stresses Stress, either physiological, biological or psychological, is an organism's response to a stressor such as an environmental condition. Stress is the body's method of reacting to a condition such as a threat, challenge or physical and psycholog ...

such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 (p38α) and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 (MKK6) and SERK1 (MKK4), MAPKKs that activate CSBP2 (p38α) and JNK, respectively but cannot phosphorylate PRKMK1 (MKK1), an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the p38 MAPK pathway, and a minor mediator of the JNK pathway. Two alternatively spliced transcripts encoding distinct isoforms have been described.

Interactions

MAP3K4 has been shown to interact with

GADD45G Growth arrest and DNA-damage-inducible protein GADD45 gamma is a protein that in humans is encoded by the ''GADD45G'' gene on chromosome 9. GADD45G is also known as CR6, DDIT2, GRP17, OIG37, and GADD45gamma. GADD45G is involved in several differen ...

, GADD45B and

GADD45A Growth arrest and DNA-damage-inducible protein GADD45 alpha is a protein that in humans is encoded by the ''GADD45A'' gene. Function This gene is a member of a group of genes, the GADD45 genes, whose transcript levels are increased following st ...

Interactions

References

Further reading