MAP3K4

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]

Full Name

mitogen-activated protein kinase kinase kinase 4

Function

Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6.

Biological Process

Chorionic trophoblast cell differentiationIEA:Ensembl
Intracellular signal transductionISS:UniProtKB
Male germ-line sex determinationIEA:Ensembl
MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Placenta developmentIEA:Ensembl
Positive regulation of JUN kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of p38MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of telomerase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of telomere cappingManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of telomere maintenance via telomeraseManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of gene expressionIEA:Ensembl
Response to UV-CManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Cytoplasm, perinuclear region
Localized in perinuclear vesicular-like structures, probably Golgi-associated vesicles.