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MAPKAPK2 - Wikipedia

From Wikipedia, the free encyclopedia

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)^[1]

Band	1q32.1	Start	206,684,905 bp^[1]
Band	1q32.1	End	206,734,281 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 1 (mouse)^[2]

Band	1\|1 E4	Start	130,981,437 bp^[2]
Band	1\|1 E4	End	131,025,563 bp^[2]

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

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

MAP kinase-activated protein kinase 2 is an enzyme that in humans is encoded by the MAPKAPK2 gene.^[5]^[6]^[7]

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.^[8]

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^[9] and vimentin remodeling. Activation of MK2 via its phosphorylation by p38 has been shown to restore the vascular barrier^[7] and repair vascular leak,^[10] associated with over 60 medical conditions, including Acute Respiratory Distress Syndrome (ARDS), a major cause of death around the world.^[11]

SASP initiation

MAPKAPK2 mediates the initiation of the senescence-associated secretory phenotype (SASP) by mTOR (mechanistic target of rapamycin).^[12]^[13] 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.^[14]^[15] Translation of mRNA for IL1A is highly dependent upon mTOR activity.^[16] mTOR activity increases levels of IL1A, mediated by MAPKAPK2.^[14]

Interactions

MAPKAPK2 has been shown to interact with:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000162889 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000016528 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Zu YL, Wu F, Gilchrist A, et al. (April 1994). "The primary structure of a human MAP kinase activated protein kinase 2". Biochemical and Biophysical Research Communications. 200 (2): 1118–24. doi:10.1006/bbrc.1994.1566. PMID 8179591.
^ Stokoe D, Caudwell B, Cohen PT, et al. (December 1993). "The substrate specificity and structure of mitogen-activated protein (MAP) kinase-activated protein kinase-2". The Biochemical Journal. 296 ( Pt 3) (Pt 3): 843–9. doi:10.1042/bj2960843. PMC 1137771. PMID 8280084.
^ ^a ^b ^c Liu T, Warburton RR, Hill NS, et al. (August 2015). "Anthrax lethal toxin-induced lung injury and treatment by activating MK2". Journal of Applied Physiology. 119 (4): 412–9. doi:10.1152/japplphysiol.00335.2015. PMC 4538279. PMID 26066827.
^ "Entrez Gene: MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2".
^ Sousa AM, Liu T, Guevara O, et al. (April 2007). "Smooth muscle alpha-actin expression and myofibroblast differentiation by TGFbeta are dependent upon MK2". Journal of Cellular Biochemistry. 100 (6): 1581–92. doi:10.1002/jcb.21154. PMC 2586991. PMID 17163490.
^ Liu T, Milia E, Warburton RR, et al. (April 2012). "Anthrax lethal toxin disrupts the endothelial permeability barrier through blocking p38 signaling". Journal of Cellular Physiology. 227 (4): 1438–45. doi:10.1002/jcp.22859. PMC 4254851. PMID 21618534.
^ Pham T, Rubenfeld GD (April 2017). "Fifty Years of Research in ARDS. The Epidemiology of Acute Respiratory Distress Syndrome. A 50th Birthday Review". American Journal of Respiratory and Critical Care Medicine. 195 (7): 860–870. doi:10.1164/rccm.201609-1773CP. PMID 28157386. S2CID 23293950.
^ Yessenkyzy A, Saliev T, Zhanaliyeva M, et al. (May 2020). "Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research". Nutrients. 12 (5): 1344. doi:10.3390/nu12051344. PMC 7285205. PMID 32397145.
^ Papadopoli D, Boulay K, Kazak L, et al. (2019). "mTOR as a central regulator of lifespan and aging". F1000Research. 8: 998. doi:10.12688/f1000research.17196.1. PMC 6611156. PMID 31316753.
^ ^a ^b Laberge RM, Sun Y, Orjalo AV, et al. (August 2015). "MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation". Nature Cell Biology. 17 (8): 1049–61. doi:10.1038/ncb3195. PMC 4691706. PMID 26147250.
^ Wang R, Yu Z, Sunchu B, et al. (June 2017). "Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism". Aging Cell. 16 (3): 564–574. doi:10.1111/acel.12587. PMC 5418203. PMID 28371119.
^ Wang R, Sunchu B, Perez VI (August 2017). "Rapamycin and the inhibition of the secretory phenotype". Experimental Gerontology. 94: 89–92. doi:10.1016/j.exger.2017.01.026. PMID 28167236. S2CID 4960885.
^ ^a ^b Rane MJ, Coxon PY, Powell DW, et al. (February 2001). "p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils". The Journal of Biological Chemistry. 276 (5): 3517–23. doi:10.1074/jbc.M005953200. PMID 11042204.
^ Janknecht R (November 2001). "Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase 2". The Journal of Biological Chemistry. 276 (45): 41856–61. doi:10.1074/jbc.M106630200. PMID 11551945.
^ ^a ^b Yannoni YM, Gaestel M, Lin LL (April 2004). "P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity". FEBS Letters. 564 (1–2): 205–11. doi:10.1016/S0014-5793(04)00351-5. PMID 15094067. S2CID 43606580.
^ Dondelinger Y, Delanghe T, Rojas-Rivera D, et al. (October 2017). "MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death". Nature Cell Biology. 19 (10): 1237–1247. doi:10.1038/ncb3608. PMID 28920952. S2CID 25779284.

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.

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 mTOR EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1
Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3 PDK4
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) kinase (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 Aurora C 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 CAMK1A CAMK1B CAMK1D CAMK1G CAMK2 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

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

This article on a gene on human chromosome 1 is a stub. You can help Wikipedia by expanding it.

Categories:

Hidden categories:

Function

Vascular barrier

SASP initiation

See also

Interactions

References

Further reading