MAP2K3

The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]

Mitogen-Activated Protein Kinase Kinase 3

Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14.

Cardiac muscle contractionIEA:Ensembl
Cellular response to lipopolysaccharideIEA:Ensembl
Cellular response to sorbitolIEA:Ensembl
Cellular response to vascular endothelial growth factor stimulusManual Assertion Based On ExperimentIMP:BHF-UCL
Cellular senescenceTAS:Reactome
Heart developmentIEA:Ensembl
Inflammatory responseIEA:Ensembl
MAPK cascadeManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of hippo signalingManual Assertion Based On ExperimentIMP:FlyBase
p38MAPK cascadeManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of blood vessel endothelial cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of MAPK cascadeIEA:Ensembl
Positive regulation of nitric-oxide synthase biosynthetic processIEA:Ensembl
Positive regulation of protein kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cytokine productionIEA:Ensembl
Response to ischemiaIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc

Cytosol
Membrane
Nucleoplasm

Defects in MAP2K3 may be involved in colon cancer.

Autophosphorylated. Phosphorylation on Ser-218 and Thr-222 by MAP kinase kinase kinases regulates positively the kinase activity (PubMed:8622669).
Phosphorylated by TAOK2 (PubMed:11279118).
(Microbial infection) Yersinia YopJ may acetylate Ser/Thr residues, preventing phosphorylation and activation, thus blocking the MAPK signaling pathway.