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mitogen-activated protein kinase kinase kinase 4 (MAP3K4)

Target Class
Kinase
Family
STE
Official Symbol
MAP3K4
Entrez Gene ID
4216
Species
Human
Accession Number
NP_005913.2
Alias Names
MAP three kinase 1; MAP/ERK kinase kinase 4; MAPK/ERK kinase kinase 4; MAPKKK4; MEK kinase 4; MEKK 4; MEKK4; MTK1; PRO0412; SSK2/SSK22 MAP kinase kinase kinase, yeast, homolog of; dJ473J16.1 (mitogen-activated protein kinase kinase kinase 4); mitogen-activated protein kinase kinase kinase 4; predicted protein of HQ0412
Background
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 and JNK MAPKs are activated by environmental stresses 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 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Two alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
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