MAPKAPK2

MAPKAPK2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	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
Identifikatori
Aliasi	MAPKAPK2
Vanjski ID-jevi	OMIM: 602006 MGI: 109298 HomoloGene: 56412 GeneCards: MAPKAPK2
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	206,734,281 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	131,025,563 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• calmodulin-dependent protein kinase activity; • signal transducer activity; • nucleotide binding; • aktivnost sa transferazom; • kinase activity; • calcium-dependent protein serine/threonine kinase activity; • calmodulin binding; • ATP binding; • GO:0001948, GO:0016582 vezivanje za proteine; • protein kinase activity; • protein serine/threonine kinase activity; • mitogen-activated protein kinase binding;
Ćelijska komponenta	• Egzosom; • citosol; • centrosom; • nukleoplazma; • citoplazma; • jedro;
Biološki proces	• response to stress; • MAPK cascade; • regulation of mRNA stability; • response to cytokine; • GO:0035404 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; • Fosforilacija; • 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; • GO:0007243 intracellular signal transduction;
	Izvori:Amigo / QuickGO
Ortolozi
	9261
	17164
	ENSG00000162889
	ENSMUSG00000016528
	P49137
	P49138
	NM_004759; NM_032960
	NM_008551
	NP_004750; NP_116584
	NP_032577
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

MAP kinaza-aktivirana protein-kinazom 2 jest enzim koji je kod ljudi kodiran genom MAPKAPK2 sa hromosoma 1^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 400 aminokiselina, a molekulska težina 45.568 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MLSNSQGQSP	PVPFPAPAPP	PQPPTPALPH	PPAQPPPPPP	QQFPQFHVKS
GLQIKKNAII	DDYKVTSQVL	GLGINGKVLQ	IFNKRTQEKF	ALKMLQDCPK
ARREVELHWR	ASQCPHIVRI	VDVYENLYAG	RKCLLIVMEC	LDGGELFSRI
QDRGDQAFTE	REASEIMKSI	GEAIQYLHSI	NIAHRDVKPE	NLLYTSKRPN
AILKLTDFGF	AKETTSHNSL	TTPCYTPYYV	APEVLGPEKY	DKSCDMWSLG
VIMYILLCGY	PPFYSNHGLA	ISPGMKTRIR	MGQYEFPNPE	WSEVSEEVKM
LIRNLLKTEP	TQRMTITEFM	NHPWIMQSTK	VPQTPLHTSR	VLKEDKERWE
DVKEEMTSAL	ATMRVDYEQI	KIKKIEDASN	PLLLKRRKKA	RALEAAALAH

Funkcija

Ovaj gen kodira člana porodice Ser/Thr protein kinaze. Ova kinaza regulirana je direktnom fosforilacijom, pomoću p38 MAP-kinaza. Poznato je da je, zajedno sa p38 MAP-kinazom, ova kinaza uključena u mnoge ćelijske procese, kao što su stres i upalne odgovore, jedarni eksport, regulaciju ekspresije gena i proliferaciju ćelija. Pokazalo se da je protein toplotnog šoka HSP27 njegov glavni direktni supstrat in vivo. Za ovaj gen su pronađene dvije varijante transkripta koje kodiraju dvije različite izoforme.^[9]

Vaskularna barijera

Pokazalo se da put MK2 ima ključnu ulogu u održavanju i popravljanju integriteta endotelne barijere u plućima putem aktina ^[10] i remodeliranja vimentina. Pokazalo se da aktivacija MK2 putem njegove fosforilacije pomoću p38 obnavlja vaskularnu barijeru^[7] i popravlja vaskularno curenje,^[11] povezano sa preko 60 medicinskih stanja, uključujući sindrom akutnog respiratornog distresa (ARDS), glavnog uzroka smrti širom svijeta.^[12]

Inicijacija SASP-a

MAPKAPK2 posreduje u inicijaciji sekretornog fenotipa vezanog za starenje (SASP), pomoću mTOR (mehanička meta rapamicina).^[13]^[14] Interleukin 1 alfa (IL1A) nalazi se na površini senescentnih ćelija, gdje doprinosi proizvodnji SASP faktora zbog pozitivne povratne petlje sa NF-κB.^[15]^[16] Translacija iRNK za IL1A u velikoj mjeri ovisi o aktivnosti mTOR-a.^[17] Aktivnost mTOR povećava nivoe IL1A, posredovane putem MAPKAPK2.^[15]

Također pogledajte

SB 203580

Interakcije

Pokazalo se da MAPKAPK2 ima interakcije sa:

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000162889 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000016528 - Ensembl, maj 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, Ai Y, Labadia ME, Huang CK (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, Cohen P (decembar 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 Liu T, Warburton RR, Hill NS, Kayyali US (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.
^ "UniProt, P49137" (jezik: engleski). Pristupljeno 13. 12. 2021.
^ "Entrez Gene: MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2".
^ Sousa AM, Liu T, Guevara O, Stevens J, Fanburg BL, Gaestel M, 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, Hill NS, Gaestel M, Kayyali US (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, Masoud AR, Umbayev B, Sergazy S, et al. (maj 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, Pollak M, Mallette F, Topisirovic I, Hulea L (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, Patil CK, Freund A, Zhou L, 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, Shoaf J, Dang I, Zhao S, et al. (juni 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, Webster R, Klein JB, Pierce W, et al. (februar 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 (novembar 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.
^ Dondelinger Y, Delanghe T, Rojas-Rivera D, Priem D, Delvaeye T, Bruggeman I, et al. (oktobar 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.

Dopunska literatura

Kapopara PR, von Felden J, Soehnlein O, Wang Y, Napp LC, Sonnenschein K, et al. (decembar 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.
Ben-Levy R, Hooper S, Wilson R, Paterson HF, Marshall CJ (septembar 1998). "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2". Current Biology. 8 (19): 1049–57. doi:10.1016/S0960-9822(98)70442-7. PMID 9768359. S2CID 15627349.
Stokoe D, Engel K, Campbell DG, Cohen P, Gaestel M (novembar 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 (novembar 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, Kotlyarov A, Plath K, Hahn M, et al. (novembar 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, Weber LA, Landry J (januar 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, Le Bourdellès B, Mallet J, Haavik J, Cohen P (oktobar 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, Buchner J, Gaestel M (januar 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, Jones E, Cowley S, Hsuan J, Saklatvala J (septembar 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, Ginty DD, Chen RH, Blenis J, Greenberg ME (oktobar 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, Plaisance S, Lee JC, Haegeman G, 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, Attwood P, Morrice N, Marshall CJ, Cohen P (decembar 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, Cariati S, Cohen P, Comb MJ (septembar 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, Jongstra J (januar 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, Furuya W, Grinstein S (januar 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 (juni 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, Saklatvala J, Krebs EG, Clark EA (oktobar 1998). "p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes". Journal of Immunology. 161 (7): 3225–36. PMID 9759836.
Heidenreich O, Neininger A, Schratt G, Zinck R, Cahill MA, Engel K, et al. (maj 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.

Vanjski linkovi

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000162889 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000016528 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8179591-5] Zu YL, Wu F, Gilchrist A, Ai Y, Labadia ME, Huang CK (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.

[pmid8280084-6] Stokoe D, Caudwell B, Cohen PT, Cohen P (decembar 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.

[Liu_412–419-7] Liu T, Warburton RR, Hill NS, Kayyali US (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.

[UniProt-8] "UniProt, P49137" (jezik: engleski). Pristupljeno 13. 12. 2021.

[entrez-9] "Entrez Gene: MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2".

[10] Sousa AM, Liu T, Guevara O, Stevens J, Fanburg BL, Gaestel M, 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.

[11] Liu T, Milia E, Warburton RR, Hill NS, Gaestel M, Kayyali US (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.

[12] 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.

[pmid32397145-13] Yessenkyzy A, Saliev T, Zhanaliyeva M, Masoud AR, Umbayev B, Sergazy S, et al. (maj 2020). "Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research". Nutrients. 12 (5): 1344. doi:10.3390/nu12051344. PMC 7285205. PMID 32397145.

[pmid31316753-14] Papadopoli D, Boulay K, Kazak L, Pollak M, Mallette F, Topisirovic I, Hulea L (2019). "mTOR as a central regulator of lifespan and aging". F1000Research. 8: 998. doi:10.12688/f1000research.17196.1. PMC 6611156. PMID 31316753.

[pmid26147250-15] Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, 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.

[pmid28371119-16] Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, et al. (juni 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.

[pmid28167236-17] 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.

[pmid11042204-18] Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, et al. (februar 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.

[pmid11551945-19] Janknecht R (novembar 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.

[pmid15094067-20] 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.

[21] Dondelinger Y, Delanghe T, Rojas-Rivera D, Priem D, Delvaeye T, Bruggeman I, et al. (oktobar 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.

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