MAPKAPK2

MAPKAPK2

Target · Stress-activated kinase

MAPKAPK2 MAP kinase-activated protein kinase 2 · MK2

MAPKAPK2, also known as MK2 or MAP kinase-activated protein kinase 2, is a stress-activated serine/threonine kinase that acts downstream of p38-alpha (MAPK14). It connects stress signalling to cytokine production, cytoskeletal reorganisation, cell cycle control and the DNA damage response. Browse Assay Genie's current range of MAPKAPK2 research reagents below, or read on for the biology behind the target.

Cytoplasm and nucleusStress-activated Ser/Thr kinaseRegulates TNF and IL-6 mRNAs
400 aa
Protein length
~46 kDa
Molecular weight
1q32.1
Gene locus
EC 2.7.11.1
Enzyme class
Target information

What is MAPKAPK2 (MAPK activated protein kinase 2)?

MAPKAPK2 is a stress-activated serine/threonine kinase involved in cytokine production, endocytosis, reorganisation of the cytoskeleton, cell migration, cell cycle control, chromatin remodelling, the DNA damage response and transcriptional regulation. After stress it is phosphorylated and activated by p38-alpha/MAPK14, and it then phosphorylates its substrates on serine within the motif Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue.

Many of its roles are post-transcriptional. By phosphorylating the AU-rich element-binding factors ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, MAPKAPK2 regulates the stability and translation of TNF and IL-6 mRNAs. Phosphorylation of TTP/ZFP36 promotes its binding to 14-3-3 and lowers its affinity for ARE mRNA, which blocks degradation of ARE-containing transcripts. Other substrates include HSP27/HSPB1, whose phosphorylation releases it from large small heat-shock protein oligomers and impairs their chaperone activity, HSF1, CDC25B, CDC25C, CEP131, LIMK1 and RPS6KA3. After DNA damage the kinase relocalises from the nucleus to the cytoplasm, where phosphorylation of HNRNPA0 and PARN stabilises GADD45A mRNA during the late G2/M checkpoint. It also supports toll-like receptor-induced macropinocytosis in dendritic cells by activating RPS6KA3.

The MAPKAPK2 gene encodes a member of the CAMK Ser/Thr protein kinase family within the protein kinase superfamily, and it is classed in the HGNC MAPKAPK family of MAPK activated protein kinases. Two transcript variants encoding different isoforms have been reported. The gene was previously named mitogen-activated protein kinase-activated protein kinase 2, and the mouse ortholog is Mapkapk2. MAPKAPK3 and MAPKAPK5 are related family members.

Inflammation and cytokine regulation

MAPKAPK2 controls TNF and IL-6 production post-transcriptionally through phosphorylation of AU-rich element-binding proteins, placing it within inflammatory response pathways.

p38 MAPK stress signalling

The kinase is activated by p38-alpha/MAPK14 after stress, making it a key readout of signalling downstream of p38 MAP kinase.

DNA damage and cell cycle

Following DNA damage, MAPKAPK2 moves to the cytoplasm and stabilises GADD45A mRNA, contributing to the late G2/M checkpoint.

Innate immunity and endocytosis

MAPKAPK2 is required for acute toll-like receptor-induced macropinocytosis in dendritic cells through activation of RPS6KA3.

Background

MAPKAPK2 frequently asked questions

What does MAPKAPK2 do?

MAPKAPK2 is a stress-activated serine/threonine kinase. Once activated by p38-alpha/MAPK14, it phosphorylates substrates such as HSP27/HSPB1, HSF1 and TTP/ZFP36, influencing cytokine production, cytoskeletal reorganisation, cell migration, cell cycle control and the DNA damage response.

What other names and isoforms does MAPKAPK2 have?

MAPKAPK2 is commonly called MK2, and its previous name was mitogen-activated protein kinase-activated protein kinase 2. The UniProt protein name is MAP kinase-activated protein kinase 2. NCBI Gene reports two transcript variants that encode two different isoforms.

Is MAPKAPK2 conserved, and which proteins are related?

A mouse ortholog, Mapkapk2, is recorded. In humans MAPKAPK2 belongs to the MAPKAPK family of MAPK activated protein kinases, alongside MAPKAPK3 and MAPKAPK5, and to the CAMK Ser/Thr protein kinase family. Check the datasheet of any product for its validated reactivity.

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Related targets

Other MAPK activated protein kinases, p38 pathway components, substrates and inflammatory cytokines with products at Assay Genie.

Gene and protein annotations from HGNC, NCBI Gene and UniProt P49137; product specifications from Assay Genie datasheets.

MAPKAPK2 Product listing