MAPKAPK2

MAP kinase-activated protein kinase 2 is an enzyme that in humans is encoded by the MAPKAPK2 gene.

MAPKAPK2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KWP, 1NXK, 1NY3, 2JBO, 2JBP, 2OKR, 2ONL, 2OZA, 2P3G, 2PZY, 3A2C, 3FPM, 3FYJ, 3FYK, 3GOK, 3KA0, 3KC3, 3KGA, 3M2W, 3M42, 3R2B, 3R2Y, 3R30, 3WI6, 4TYH
Identifiers
Aliases	MAPKAPK2, MAPKAP-K2, MK-2, MK2, mitogen-activated protein kinase-activated protein kinase 2, MAPK activated protein kinase 2
External IDs	OMIM: 602006; MGI: 109298; HomoloGene: 56412; GeneCards: MAPKAPK2; OMA:MAPKAPK2 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1q32.1 Start 206,684,905 bp End 206,734,281 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1|1 E4 Start 130,981,437 bp End 131,025,563 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart right auricle left ventricle gastrocnemius muscle muscle of thigh myocardium of left ventricle stromal cell of endometrium upper lobe of left lung right lung islet of Langerhans Top expressed in plantaris muscle muscle of thigh interventricular septum extensor digitorum longus muscle granulocyte soleus muscle skeletal muscle tissue myocardium of ventricle thoracic diaphragm extraocular muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calmodulin-dependent protein kinase activity signal transducer activity nucleotide binding transferase activity kinase activity calcium-dependent protein serine/threonine kinase activity calmodulin binding ATP binding protein binding protein kinase activity protein serine/threonine kinase activity mitogen-activated protein kinase binding Cellular component extracellular exosome cytosol centrosome nucleoplasm cytoplasm nucleus Biological process response to stress MAPK cascade regulation of mRNA stability response to cytokine peptidyl-serine phosphorylation cellular response to vascular endothelial growth factor stimulus mRNA stabilization protein autophosphorylation 3'-UTR-mediated mRNA stabilization cellular response to DNA damage stimulus inner ear development p38MAPK cascade Ras protein signal transduction leukotriene metabolic process regulation of cellular response to heat phosphorylation protein phosphorylation regulation of interleukin-6 production vascular endothelial growth factor receptor signaling pathway response to lipopolysaccharide inflammatory response macropinocytosis regulation of tumor necrosis factor production toll-like receptor signaling pathway intracellular signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9261 17164 Ensembl ENSG00000162889 ENSMUSG00000016528 UniProt P49137 P49138 RefSeq (mRNA) NM_004759 NM_032960 NM_008551 RefSeq (protein) NP_004750 NP_116584 NP_032577 Location (UCSC) Chr 1: 206.68 – 206.73 Mb Chr 1: 130.98 – 131.03 Mb PubMed search
Wikidata
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Function

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 its major direct substrate in vivo. Two transcript variants encoding two different isoforms have been found for this gene.

Vascular barrier

MK2 pathway has been demonstrated to have a key role in maintaining and repairing the integrity of endothelial barrier in the lung via actin and vimentin remodeling. Activation of MK2 via its phosphorylation by p38 has been shown to restore the vascular barrier and repair vascular leak, associated with over 60 medical conditions, including Acute Respiratory Distress Syndrome (ARDS), a major cause of death around the world.

SASP initiation

MAPKAPK2 mediates the initiation of the senescence-associated secretory phenotype (SASP) by mTOR (mechanistic target of rapamycin). Interleukin 1 alpha (IL1A) is found on the surface of senescent cells, where it contributes to the production of SASP factors due to a positive feedback loop with NF-κB. Translation of mRNA for IL1A is highly dependent upon mTOR activity. mTOR activity increases levels of IL1A, mediated by MAPKAPK2.

See also

• SB 203580, suppresses the activation of MAPKAPK2
• MK2-AP directly activates MAPKAPK2 independent of p38.

Interactions

MAPKAPK2 has been shown to interact with:

• AKT1,
• MAPK14,
• PHC2, and
• SHC1.
• RIPK1

Further reading

• Kapopara PR, von Felden J, Soehnlein O, et al. (December 2014). "Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury". Thrombosis and Haemostasis. 112 (6): 1264–76. doi:10.1160/TH14-02-0174. PMID 25120198. S2CID 12322445.
• Ben-Levy R, Hooper S, Wilson R, et al. (September 1998). "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2". Current Biology. 8 (19): 1049–57. Bibcode:1998CBio....8.1049B. doi:10.1016/S0960-9822(98)70442-7. PMID 9768359. S2CID 15627349.
• Stokoe D, Engel K, Campbell DG, et al. (November 1992). "Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins". FEBS Letters. 313 (3): 307–13. doi:10.1016/0014-5793(92)81216-9. PMID 1332886.
• Vulliet PR, Woodgett JR, Cohen P (November 1984). "Phosphorylation of tyrosine hydroxylase by calmodulin-dependent multiprotein kinase". The Journal of Biological Chemistry. 259 (22): 13680–3. doi:10.1016/S0021-9258(18)89798-8. PMID 6150037.
• Engel K, Schultz H, Martin F, et al. (November 1995). "Constitutive activation of mitogen-activated protein kinase-activated protein kinase 2 by mutation of phosphorylation sites and an A-helix motif". The Journal of Biological Chemistry. 270 (45): 27213–21. doi:10.1074/jbc.270.45.27213. PMID 7592979.
• Lavoie JN, Lambert H, Hickey E, et al. (January 1995). "Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27". Molecular and Cellular Biology. 15 (1): 505–16. doi:10.1128/MCB.15.1.505. PMC 232001. PMID 7799959.
• Sutherland C, Alterio J, Campbell DG, et al. (October 1993). "Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2". European Journal of Biochemistry. 217 (2): 715–22. doi:10.1111/j.1432-1033.1993.tb18297.x. PMID 7901013.
• Knauf U, Jakob U, Engel K, et al. (January 1994). "Stress- and mitogen-induced phosphorylation of the small heat shock protein Hsp25 by MAPKAP kinase 2 is not essential for chaperone properties and cellular thermoresistance". The EMBO Journal. 13 (1): 54–60. doi:10.1002/j.1460-2075.1994.tb06234.x. PMC 394778. PMID 7905823.
• Freshney NW, Rawlinson L, Guesdon F, et al. (September 1994). "Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27". Cell. 78 (6): 1039–49. doi:10.1016/0092-8674(94)90278-X. PMID 7923354. S2CID 37608621.
• Rivera VM, Miranti CK, Misra RP, et al. (October 1993). "A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity". Molecular and Cellular Biology. 13 (10): 6260–73. doi:10.1128/mcb.13.10.6260. PMC 364685. PMID 8413226.
• Beyaert R, Cuenda A, Vanden Berghe W, et al. (April 1996). "The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor". The EMBO Journal. 15 (8): 1914–23. doi:10.1002/j.1460-2075.1996.tb00542.x. PMC 450110. PMID 8617238.
• Ben-Levy R, Leighton IA, Doza YN, et al. (December 1995). "Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2". The EMBO Journal. 14 (23): 5920–30. doi:10.1002/j.1460-2075.1995.tb00280.x. PMC 394711. PMID 8846784.
• Tan Y, Rouse J, Zhang A, et al. (September 1996). "FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2". The EMBO Journal. 15 (17): 4629–42. doi:10.1002/j.1460-2075.1996.tb00840.x. PMC 452194. PMID 8887554.
• Huang CK, Zhan L, Ai Y, et al. (January 1997). "LSP1 is the major substrate for mitogen-activated protein kinase-activated protein kinase 2 in human neutrophils". The Journal of Biological Chemistry. 272 (1): 17–9. doi:10.1074/jbc.272.1.17. PMID 8995217.
• Krump E, Sanghera JS, Pelech SL, et al. (January 1997). "Chemotactic peptide N-formyl-met-leu-phe activation of p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase-2 in human neutrophils". The Journal of Biological Chemistry. 272 (2): 937–44. doi:10.1074/jbc.272.2.937. PMID 8995385.
• Engel K, Kotlyarov A, Gaestel M (June 1998). "Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation". The EMBO Journal. 17 (12): 3363–71. doi:10.1093/emboj/17.12.3363. PMC 1170674. PMID 9628873.
• Craxton A, Shu G, Graves JD, et al. (October 1998). "p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes". Journal of Immunology. 161 (7): 3225–36. doi:10.4049/jimmunol.161.7.3225. PMID 9759836. S2CID 39342790.
• Heidenreich O, Neininger A, Schratt G, et al. (May 1999). "MAPKAP kinase 2 phosphorylates serum response factor in vitro and in vivo". The Journal of Biological Chemistry. 274 (20): 14434–43. doi:10.1074/jbc.274.20.14434. PMID 10318869.