MAPKAPK2

Mitogen-activated protein kinase-activated protein kinase 2
PDB rendering based on 1kwp.
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​
Identifiers
Symbols	MAPKAPK2 ; MAPKAP-K2; MK-2; MK2
External IDs	OMIM: 602006 MGI: 109298 HomoloGene: 56412 ChEMBL: 2208 GeneCards: MAPKAPK2 Gene
EC number	2.7.11.1
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • calmodulin-dependent protein kinase activity • signal transducer activity • protein binding • calmodulin binding • ATP binding • calcium-dependent protein serine/threonine kinase activity • mitogen-activated protein kinase binding Cellular component • nucleus • nucleoplasm • cytoplasm • centrosome • cytosol • extracellular exosome Biological process • MAPK cascade • activation of MAPK activity • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • protein phosphorylation • leukotriene metabolic process • response to stress • inflammatory response • cellular response to DNA damage stimulus • Ras protein signal transduction • gene expression • peptidyl-serine phosphorylation • arachidonic acid metabolic process • G2 DNA damage checkpoint • response to lipopolysaccharide • regulation of interleukin-6 production • regulation of tumor necrosis factor production • response to cytokine • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • cellular response to heat • TRIF-dependent toll-like receptor signaling pathway • cellular response to vascular endothelial growth factor stimulus • p38MAPK cascade • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • positive regulation of tumor necrosis factor biosynthetic process • small molecule metabolic process • macropinocytosis • innate immune response • protein autophosphorylation • vascular endothelial growth factor receptor signaling pathway • neurotrophin TRK receptor signaling pathway • inner ear development • stress-activated MAPK cascade • 3'-UTR-mediated mRNA stabilization • regulation of cellular response to heat Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9261	17164
Ensembl	ENSG00000162889	ENSMUSG00000016528
UniProt	P49137	P49138
RefSeq (mRNA)	NM_004759	NM_008551
RefSeq (protein)	NP_004750	NP_032577
Location (UCSC)	Chr 1: 206.68 – 206.73 Mb	Chr 1: 131.05 – 131.1 Mb
PubMed search

MAP kinase-activated protein kinase 2 is an enzyme that in humans is encoded by the MAPKAPK2 gene.^[1][2]

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 one of the substrates of this kinase in vivo. Two transcript variants encoding two different isoforms have been found for this gene.^[3]

See also

• SB 203580, suppresses the activation of MAPKAPK2

Interactions

MAPKAPK2 has been shown to interact with:

• AKT1,^[4]
• MAPK14,^[4][5]
• PHC2,^[6] and
• SHC1.^[6]

References

1. Zu YL, Wu F, Gilchrist A, Ai Y, Labadia ME, Huang CK (Jun 1994). "The primary structure of a human MAP kinase activated protein kinase 2". Biochem Biophys Res Commun 200 (2): 1118–24. doi:10.1006/bbrc.1994.1566. PMID 8179591.
2. Stokoe D, Caudwell B, Cohen PT, Cohen P (Feb 1994). "The substrate specificity and structure of mitogen-activated protein (MAP) kinase-activated protein kinase-2". Biochem J 296 (Pt 3): 843–9. PMC 1137771. PMID 8280084.
3. "Entrez Gene: MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2".
4. Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, Ping P, McLeish KR (Feb 2001). "p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils". J. Biol. Chem. 276 (5): 3517–23. doi:10.1074/jbc.M005953200. PMID 11042204.
5. Janknecht R (Nov 2001). "Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase 2". J. Biol. Chem. 276 (45): 41856–61. doi:10.1074/jbc.M106630200. PMID 11551945.
6. Yannoni YM, Gaestel M, Lin LL (Apr 2004). "P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity". FEBS Lett. 564 (1-2): 205–11. doi:10.1016/S0014-5793(04)00351-5. PMID 15094067.

Further reading

• Kapopara PR, von Felden J, Soehnlein O, Wang Y, Napp LC, Sonnenschein K, Wollert KC, Schieffer B, Gaestel M, Bauersachs J, Bavendiek U (2014). "Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury". Thromb Haemost. 112 (6): 1–13. doi:10.1160/TH14-02-0174. PMID 25120198.
• Ben-Levy R, Hooper S, Wilson R, Paterson HF, Marshall CJ (1999). "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2". Curr. Biol. 8 (19): 1049–57. doi:10.1016/S0960-9822(98)70442-7. PMID 9768359.
• Stokoe D, Engel K, Campbell DG, Cohen P, Gaestel M (1992). "Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins". FEBS Lett. 313 (3): 307–13. doi:10.1016/0014-5793(92)81216-9. PMID 1332886.
• Vulliet PR, Woodgett JR, Cohen P (1984). "Phosphorylation of tyrosine hydroxylase by calmodulin-dependent multiprotein kinase". J. Biol. Chem. 259 (22): 13680–3. PMID 6150037.
• Engel K, Schultz H, Martin F, Kotlyarov A, Plath K, Hahn M, Heinemann U, Gaestel M (1995). "Constitutive activation of mitogen-activated protein kinase-activated protein kinase 2 by mutation of phosphorylation sites and an A-helix motif". J. Biol. Chem. 270 (45): 27213–21. doi:10.1074/jbc.270.45.27213. PMID 7592979.
• Lavoie JN, Lambert H, Hickey E, Weber LA, Landry J (1995). "Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27". Mol. Cell. Biol. 15 (1): 505–16. PMC 232001. PMID 7799959.
• Sutherland C, Alterio J, Campbell DG, Le Bourdellès B, Mallet J, Haavik J, Cohen P (1993). "Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2". Eur. J. Biochem. 217 (2): 715–22. doi:10.1111/j.1432-1033.1993.tb18297.x. PMID 7901013.
• Knauf U, Jakob U, Engel K, Buchner J, Gaestel M (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". EMBO J. 13 (1): 54–60. PMC 394778. PMID 7905823.
• Freshney NW, Rawlinson L, Guesdon F, Jones E, Cowley S, Hsuan J, Saklatvala J (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.
• Rivera VM, Miranti CK, Misra RP, Ginty DD, Chen RH, Blenis J, Greenberg ME (1993). "A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity". Mol. Cell. Biol. 13 (10): 6260–73. PMC 364685. PMID 8413226.
• Beyaert R, Cuenda A, Vanden Berghe W, Plaisance S, Lee JC, Haegeman G, Cohen P, Fiers W (1996). "The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor". EMBO J. 15 (8): 1914–23. PMC 450110. PMID 8617238.
• Ben-Levy R, Leighton IA, Doza YN, Attwood P, Morrice N, Marshall CJ, Cohen P (1996). "Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2". EMBO J. 14 (23): 5920–30. PMC 394711. PMID 8846784.
• Tan Y, Rouse J, Zhang A, Cariati S, Cohen P, Comb MJ (1997). "FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2". EMBO J. 15 (17): 4629–42. PMC 452194. PMID 8887554.
• Huang CK, Zhan L, Ai Y, Jongstra J (1997). "LSP1 is the major substrate for mitogen-activated protein kinase-activated protein kinase 2 in human neutrophils". J. Biol. Chem. 272 (1): 17–9. doi:10.1074/jbc.272.1.17. PMID 8995217.
• Krump E, Sanghera JS, Pelech SL, Furuya W, Grinstein S (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". J. Biol. Chem. 272 (2): 937–44. doi:10.1074/jbc.272.2.937. PMID 8995385.
• Engel K, Kotlyarov A, Gaestel M (1998). "Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation". EMBO J. 17 (12): 3363–71. doi:10.1093/emboj/17.12.3363. PMC 1170674. PMID 9628873.
• Craxton A, Shu G, Graves JD, Saklatvala J, Krebs EG, Clark EA (1998). "p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes". J. Immunol. 161 (7): 3225–36. PMID 9759836.
• Heidenreich O, Neininger A, Schratt G, Zinck R, Cahill MA, Engel K, Kotlyarov A, Kraft R, Kostka S, Gaestel M, Nordheim A (1999). "MAPKAP kinase 2 phosphorylates serum response factor in vitro and in vivo". J. Biol. Chem. 274 (20): 14434–43. doi:10.1074/jbc.274.20.14434. PMID 10318869.