MAPKAPK2

Mitogen-activated protein kinase-activated protein kinase 2

PDB rendering based on 1kwp.

Available structures
PDB	1KWP, 1NXK, 1NY3, 2JBO, 2JBP, 2OKR, 2ONL, 2OZA, 2P3G, 2PZY, 3A2C, 3FPM, 3FYJ, 3FYK, 3KA0, 3KC3, 3KGA, 3M2W

Identifiers

Symbols

MAPKAPK2;

External IDs

OMIM: 602006 MGI: 109298 HomoloGene: 56412 GeneCards: MAPKAPK2 Gene

EC number

2.7.11.1

Gene Ontology
Molecular function	• nucleotide binding • protein kinase activity • protein serine/threonine kinase activity • protein serine/threonine kinase activity • signal transducer activity • protein binding • ATP binding
Cellular component	• nucleus • nucleoplasm • cytoplasm • cytosol • cytosol
Biological process	• MAPKKK cascade • activation of MAPK activity • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • protein phosphorylation • prostanoid metabolic process • Ras protein signal transduction • Toll signaling pathway • RNA metabolic process • mRNA metabolic process • leukotriene biosynthetic process • toll-like receptor 1 signaling pathway • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • hormone biosynthetic process • innate immune response • nerve growth factor receptor signaling pathway • mRNA stabilization • stress-activated MAPK cascade
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 1:
206.86 – 206.91 Mb

Chr 1:
132.95 – 132.99 Mb

PubMed search

[1]

[2]

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

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]

1 See also
2 Interactions
3 References
4 Further reading

Interactions

MAPKAPK2 has been shown to interact with MAPK14,^[4]^[5] AKT1,^[4] PHC2^[6] and SHC1.^[6]

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) (Pt 3): 843–9. PMC 1137771. PMID 8280084. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1137771.
^ "Entrez Gene: MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9261.
^ ^a ^b Rane, M J; Coxon P Y, Powell D W, Webster R, Klein J B, Pierce W, Ping P, McLeish K R (Feb. 2001). "p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils". J. Biol. Chem. (United States) 276 (5): 3517–23. doi:10.1074/jbc.M005953200. ISSN 0021-9258. 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. (United States) 276 (45): 41856–61. doi:10.1074/jbc.M106630200. ISSN 0021-9258. PMID 11551945.
^ ^a ^b Yannoni, Yvonne M; Gaestel Matthias, Lin Lih-Ling (Apr. 2004). "P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity". FEBS Lett. (Netherlands) 564 (1–2): 205–11. doi:10.1016/S0014-5793(04)00351-5. ISSN 0014-5793. PMID 15094067.

Ben-Levy R, Hooper S, Wilson R, et al. (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, et al. (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, et al. (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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=232001.
Sutherland C, Alterio J, Campbell DG, et al. (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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=394778.
Freshney NW, Rawlinson L, Guesdon F, et al. (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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=364685.
Beyaert R, Cuenda A, Vanden Berghe W, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=450110.
Ben-Levy R, Leighton IA, Doza YN, et al. (1996). "Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2". EMBO J. 14 (23): 5920–30. PMC 394711. PMID 8846784. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=394711.
Tan Y, Rouse J, Zhang A, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=452194.
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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170674.
Craxton A, Shu G, Graves JD, et al. (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, et al. (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

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, CDC2L5, CRKRS, 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

B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6

MAPKAPK2

Contents

See also

Interactions

References

Further reading