MAPKAPK2

Mitogen-activated protein kinase-activated protein kinase 2

PDB rendering based on 1kwp.

Available structures

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

RefSeq (mRNA)

RefSeq (protein)

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]

Interactions

MAPKAPK2 has been shown to interact with:

References

↑ 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.
↑ 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.
↑ "Entrez Gene: MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2".
1 2 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.
↑ 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.
1 2 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.

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.

PDB gallery

1kwp: Crystal Structure of MAPKAP2

1nxk: Crystal structure of staurosporine bound to MAP KAP kinase 2

1ny3: Crystal structure of ADP bound to MAP KAP kinase 2

2jbo: PROTEIN KINASE MK2 IN COMPLEX WITH AN INHIBITOR (CRYSTAL FORM-1, SOAKING)

2jbp: PROTEIN KINASE MK2 IN COMPLEX WITH AN INHIBITOR (CRYSTAL FORM-2, CO-CRYSTALLIZATION)

2onl: Crystal Structure of the p38a-MAPKAP kinase 2 Heterodimer

2oza: Structure of p38alpha complex

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated Mammalian target of rapamycin EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3

(3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)) (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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MAPKAPK2

Function

See also

Interactions

References

Further reading