MAPKAPK2

This gene encodes a member of the Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by p38 MAP kinase. In conjunction with p38 MAP kinase, this kinase is known to be involved in many cellular processes including stress and inflammatory responses, nuclear export, gene expression regulation and cell proliferation. Heat shock protein HSP27 was shown to be one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Mitogen-Activated Protein Kinase-Activated Protein Kinase 2

Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218).
Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734).
Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.

3'-UTR-mediated mRNA stabilizationManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to DNA damage stimulusManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to vascular endothelial growth factor stimulusManual Assertion Based On ExperimentIMP:BHF-UCL
Inflammatory responseISS:UniProtKB
Inner ear developmentIEA:Ensembl
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Leukotriene metabolic processTAS:Reactome
MacropinocytosisISS:UniProtKB
MAPK cascadeManual Assertion Based On ExperimentTAS:ProtInc
p38MAPK cascadeIEA:Ensembl
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of tumor necrosis factor productionIEA:Ensembl
Protein autophosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Protein phosphorylationManual Assertion Based On ExperimentTAS:ProtInc
Regulation of cellular response to heatTAS:Reactome
Regulation of interleukin-6 productionISS:UniProtKB
Regulation of mRNA stabilityTAS:Reactome
Regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIDA:UniProtKB
Response to cytokineManual Assertion Based On ExperimentIDA:UniProtKB
Response to lipopolysaccharideISS:UniProtKB
Toll-like receptor signaling pathwayISS:UniProtKB
Vascular endothelial growth factor receptor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL

Cytoplasm
Nucleus
Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm.

Sumoylation inhibits the protein kinase activity.
Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-222, Ser-272 and Thr-334.