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{{Infokutija gen}}
'''MAP [[kinaza]]-aktivirana protein-kinazom 2''' jest [[enzim]] koji je kod [[ljudi]] [[kodon|kodiran]] [[gen]]om '''MAPKAPK2''' sa  [[hromosom 1|hromosoma 1]]<ref name="pmid8179591">{{cite journal | vauthors = Zu YL, Wu F, Gilchrist A, Ai Y, Labadia ME, Huang CK | title = The primary structure of a human MAP kinase activated protein kinase 2 | journal = Biochemical and Biophysical Research Communications | volume = 200 | issue = 2 | pages = 1118–24 | date = april 1994 | pmid = 8179591 | doi = 10.1006/bbrc.1994.1566 }}</ref><ref name="pmid8280084">{{cite journal | vauthors = Stokoe D, Caudwell B, Cohen PT, Cohen P | title = The substrate specificity and structure of mitogen-activated protein (MAP) kinase-activated protein kinase-2 | journal = The Biochemical Journal | volume = 296 ( Pt 3) | issue = Pt 3 | pages = 843–9 | date = decembar 1993 | pmid = 8280084 | pmc = 1137771 | doi = 10.1042/bj2960843 }}</ref><ref name="Liu 412–419">{{cite journal | vauthors = Liu T, Warburton RR, Hill NS, Kayyali US | title = Anthrax lethal toxin-induced lung injury and treatment by activating MK2 | journal = Journal of Applied Physiology | volume = 119 | issue = 4 | pages = 412–9 | date = august 2015 | pmid = 26066827 | pmc = 4538279 | doi = 10.1152/japplphysiol.00335.2015 }}</ref>

==Aminokiselinska sekvenca==	
Dužina [[polipeptid]]nog lanca je 400 [[aminokiselina]], a [[molekularna masa|molekulska težina]] 45.568 [[dalton (jedinica)|Da]].<ref name="UniProt">{{cite web|url=http://www.uniprot.org/uniprot/P49137#sequences |title=UniProt, P49137 |language=en |access-date=13. 12. 2021}}</ref>
{{legenda aminokiselina}}
<table  style="font-family:monospace;">
<tr style="text-align:right;"><th>10</th><th></th><th>20</th><th></th><th>30</th><th></th><th>40</th><th></th><th>50</th></tr>
<tr style="background-color: #eee;"><td>MLSNSQGQSP</td><td style="background-color: #f9f9f9;"></td><td>PVPFPAPAPP</td><td style="background-color: #f9f9f9;"></td><td>PQPPTPALPH</td><td style="background-color: #f9f9f9;"></td><td>PPAQPPPPPP</td><td style="background-color: #f9f9f9;"></td><td>QQFPQFHVKS</td></tr>
<tr style="background-color: #eee;"><td>GLQIKKNAII</td><td style="background-color: #f9f9f9;"></td><td>DDYKVTSQVL</td><td style="background-color: #f9f9f9;"></td><td>GLGINGKVLQ</td><td style="background-color: #f9f9f9;"></td><td>IFNKRTQEKF</td><td style="background-color: #f9f9f9;"></td><td>ALKMLQDCPK</td></tr>
<tr style="background-color: #eee;"><td>ARREVELHWR</td><td style="background-color: #f9f9f9;"></td><td>ASQCPHIVRI</td><td style="background-color: #f9f9f9;"></td><td>VDVYENLYAG</td><td style="background-color: #f9f9f9;"></td><td>RKCLLIVMEC</td><td style="background-color: #f9f9f9;"></td><td>LDGGELFSRI</td></tr>
<tr style="background-color: #eee;"><td>QDRGDQAFTE</td><td style="background-color: #f9f9f9;"></td><td>REASEIMKSI</td><td style="background-color: #f9f9f9;"></td><td>GEAIQYLHSI</td><td style="background-color: #f9f9f9;"></td><td>NIAHRDVKPE</td><td style="background-color: #f9f9f9;"></td><td>NLLYTSKRPN</td></tr>
<tr style="background-color: #eee;"><td>AILKLTDFGF</td><td style="background-color: #f9f9f9;"></td><td>AKETTSHNSL</td><td style="background-color: #f9f9f9;"></td><td>TTPCYTPYYV</td><td style="background-color: #f9f9f9;"></td><td>APEVLGPEKY</td><td style="background-color: #f9f9f9;"></td><td>DKSCDMWSLG</td></tr>
<tr style="background-color: #eee;"><td>VIMYILLCGY</td><td style="background-color: #f9f9f9;"></td><td>PPFYSNHGLA</td><td style="background-color: #f9f9f9;"></td><td>ISPGMKTRIR</td><td style="background-color: #f9f9f9;"></td><td>MGQYEFPNPE</td><td style="background-color: #f9f9f9;"></td><td>WSEVSEEVKM</td></tr>
<tr style="background-color: #eee;"><td>LIRNLLKTEP</td><td style="background-color: #f9f9f9;"></td><td>TQRMTITEFM</td><td style="background-color: #f9f9f9;"></td><td>NHPWIMQSTK</td><td style="background-color: #f9f9f9;"></td><td>VPQTPLHTSR</td><td style="background-color: #f9f9f9;"></td><td>VLKEDKERWE</td></tr>
<tr style="background-color: #eee;"><td>DVKEEMTSAL</td><td style="background-color: #f9f9f9;"></td><td>ATMRVDYEQI</td><td style="background-color: #f9f9f9;"></td><td>KIKKIEDASN</td><td style="background-color: #f9f9f9;"></td><td>PLLLKRRKKA</td><td style="background-color: #f9f9f9;"></td><td>RALEAAALAH</td></tr>
<tr style="background-color: #eee;"><td></td></tr>
</table>

== Funkcija ==

Ovaj gen kodira člana porodice [[Ser/Thr protein kinaze]]. Ova [[kinaza]] regulirana je direktnom [[fosfolilacija|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 [[upala|upalne]] odgovore, jedarni eksport, regulaciju [[ekspresije gena]] i [[ćelijska proliferacija|proliferaciju ćelija]]. Pokazalo se da je [[protein toplotnog šoka]] [[HSP27]] njegov glavni direktni [[supstrat (biohemija)|supstrat]] ''[[in vivo]]''. Za ovaj gen su pronađene dvije [[varijante transkripta]] koje kodiraju dvije različite [[izoforme]].<ref name="entrez">{{cite web | title = Entrez Gene: MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9261}}</ref>

=== Vaskularna barijera ===
Pokazalo se da put MK2 ima ključnu ulogu u održavanju i popravljanju integriteta [[endotel]]ne barijere u [[pluća|plućima]] putem [[aktin]]a <ref>{{cite journal | vauthors = Sousa AM, Liu T, Guevara O, Stevens J, Fanburg BL, Gaestel M, Toksoz D, Kayyali US | display-authors = 6 | title = Smooth muscle alpha-actin expression and myofibroblast differentiation by TGFbeta are dependent upon MK2 | journal = Journal of Cellular Biochemistry | volume = 100 | issue = 6 | pages = 1581–92 | date = april 2007 | pmid = 17163490 | pmc = 2586991 | doi = 10.1002/jcb.21154 }}</ref> i remodeliranja vimentina. Pokazalo se da aktivacija MK2 putem njegove [[fosforilacije]] pomoću p38 obnavlja vaskularnu barijeru<ref name="Liu 412–419"/> i popravlja vaskularno curenje,<ref>{{cite journal | vauthors = Liu T, Milia E, Warburton RR, Hill NS, Gaestel M, Kayyali US | title = Anthrax lethal toxin disrupts the endothelial permeability barrier through blocking p38 signaling | journal = Journal of Cellular Physiology | volume = 227 | issue = 4 | pages = 1438–45 | date = april 2012 | pmid = 21618534 | pmc = 4254851 | doi = 10.1002/jcp.22859 }}</ref> povezano sa preko 60 medicinskih stanja, uključujući sindrom akutnog respiratornog distresa ([[Sindrom akutnog respiratornog distresa|ARDS]]), glavnog uzroka smrti širom svijeta.<ref>{{cite journal | vauthors = Pham T, Rubenfeld GD | title = Fifty Years of Research in ARDS. The Epidemiology of Acute Respiratory Distress Syndrome. A 50th Birthday Review | journal = American Journal of Respiratory and Critical Care Medicine | volume = 195 | issue = 7 | pages = 860–870 | date = april 2017 | pmid = 28157386 | doi = 10.1164/rccm.201609-1773CP | s2cid = 23293950 }}</ref>

=== Inicijacija SASP-a ===
MAPKAPK2 posreduje u inicijaciji [[SASP|sekretornog fenotipa vezanog za starenje]] (SASP), pomoću [[mTOR]] (mehanička meta rapamicina).<ref name="pmid32397145">{{cite journal | vauthors = Yessenkyzy A, Saliev T, Zhanaliyeva M, Masoud AR, Umbayev B, Sergazy S, Krivykh E, Gulyayev A, Nurgozhin T | display-authors = 6 | title = Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research | journal = Nutrients | volume = 12 | issue = 5 | pages = 1344 | date = maj 2020 | pmid = 32397145 | pmc = 7285205 | doi = 10.3390/nu12051344 | doi-access = free }}</ref><ref name="pmid31316753">{{cite journal | vauthors = Papadopoli D, Boulay K, Kazak L, Pollak M, Mallette F, Topisirovic I, Hulea L | title = mTOR as a central regulator of lifespan and aging | journal = F1000Research | volume = 8 | page = 998 | year = 2019 | pmid = 31316753 | pmc = 6611156 | doi = 10.12688/f1000research.17196.1 }}</ref>  [[IL1A|Interleukin 1 alfa]] (IL1A) nalazi se na površini [[starenje|senescentnih]] ćelija, gdje doprinosi proizvodnji SASP faktora zbog [[povratna informacija|pozitivne povratne petlje]] sa NF-κB.<ref name="pmid26147250">{{cite journal | vauthors = Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, Curran SC, Davalos AR, Wilson-Edell KA, Liu S, Limbad C, Demaria M, Li P, Hubbard GB, Ikeno Y, Javors M, Desprez PY, Benz CC, Kapahi P, Nelson PS, Campisi J | display-authors = 6 | title = MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation | journal = Nature Cell Biology | volume = 17 | issue = 8 | pages = 1049–61 | date = august 2015 | pmid = 26147250 | pmc = 4691706 | doi = 10.1038/ncb3195 }}</ref><ref name="pmid28371119">{{cite journal | vauthors = Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, Caples K, Bradley L, Beaver LM, Ho E, Löhr CV, Perez VI | display-authors = 6 | title = Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism | journal = Aging Cell | volume = 16 | issue = 3 | pages = 564–574 | date = juni 2017 | pmid = 28371119 | pmc = 5418203 | doi = 10.1111/acel.12587 }}</ref> Translacija [[iRNK]] za IL1A u velikoj mjeri ovisi o aktivnosti mTOR-a.<ref name="pmid28167236">{{cite journal | vauthors = Wang R, Sunchu B, Perez VI | title = Rapamycin and the inhibition of the secretory phenotype | journal = Experimental Gerontology | volume = 94 | pages = 89–92 | date = august 2017 | pmid = 28167236 | doi = 10.1016/j.exger.2017.01.026 | s2cid = 4960885 }}</ref> Aktivnost mTOR povećava nivoe IL1A, posredovane  putem MAPKAPK2.<ref name="pmid26147250" />

== Također pogledajte ==
* [[SB 203580]]

== Interakcije ==

Pokazalo se da MAPKAPK2 ima [[interakcija protein-protein|interakcije]] sa:
{{refbegin|3}}
* [[AKT1]],<ref name = pmid11042204/> 
* [[MAPK14]],<ref name = pmid11042204>{{cite journal | vauthors = Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, Ping P, McLeish KR | display-authors = 6 | title = p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils | journal = The Journal of Biological Chemistry | volume = 276 | issue = 5 | pages = 3517–23 | date = februar 2001 | pmid = 11042204 | doi = 10.1074/jbc.M005953200 | doi-access = free }}</ref><ref name = pmid11551945>{{cite journal | vauthors = Janknecht R | title = Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase 2 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 45 | pages = 41856–61 | date = novembar 2001 | pmid = 11551945 | doi = 10.1074/jbc.M106630200 | doi-access = free }}</ref> 
* [[PHC2]],<ref name = pmid15094067>{{cite journal | vauthors = Yannoni YM, Gaestel M, Lin LL | title = P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity | journal = FEBS Letters | volume = 564 | issue = 1–2 | pages = 205–11 | date = april 2004 | pmid = 15094067 | doi = 10.1016/S0014-5793(04)00351-5 | doi-access = free }}</ref> 
* [[SHC1]].<ref name = pmid15094067/>
* [[RIPK1]]<ref>{{cite journal | vauthors = Dondelinger Y, Delanghe T, Rojas-Rivera D, Priem D, Delvaeye T, Bruggeman I, Van Herreweghe F, Vandenabeele P, Bertrand MJ | display-authors = 6 | title = MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death | journal = Nature Cell Biology | volume = 19 | issue = 10 | pages = 1237–1247 | date = oktobar 2017 | pmid = 28920952 | doi = 10.1038/ncb3608 | s2cid = 25779284 }}</ref>
{{refend}}

== Reference ==
{{reflist}}

==Dopunska literatura ==
{{refbegin |33em}}
* {{cite journal | vauthors = Kapopara PR, von Felden J, Soehnlein O, Wang Y, Napp LC, Sonnenschein K, Wollert KC, Schieffer B, Gaestel M, Bauersachs J, Bavendiek U | display-authors = 6 | title = Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury | journal = Thrombosis and Haemostasis | volume = 112 | issue = 6 | pages = 1264–76 | date = decembar 2014 | pmid = 25120198 | doi = 10.1160/TH14-02-0174 | author-link10 = Johann Bauersachs }}
* {{cite journal | vauthors = Ben-Levy R, Hooper S, Wilson R, Paterson HF, Marshall CJ | title = Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2 | journal = Current Biology | volume = 8 | issue = 19 | pages = 1049–57 | date = septembar 1998 | pmid = 9768359 | doi = 10.1016/S0960-9822(98)70442-7 | s2cid = 15627349 | doi-access = free }}
* {{cite journal | vauthors = Stokoe D, Engel K, Campbell DG, Cohen P, Gaestel M | title = Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins | journal = FEBS Letters | volume = 313 | issue = 3 | pages = 307–13 | date = novembar 1992 | pmid = 1332886 | doi = 10.1016/0014-5793(92)81216-9 | doi-access = free }}
* {{cite journal | vauthors = Vulliet PR, Woodgett JR, Cohen P | title = Phosphorylation of tyrosine hydroxylase by calmodulin-dependent multiprotein kinase | journal = The Journal of Biological Chemistry | volume = 259 | issue = 22 | pages = 13680–3 | date = novembar 1984 | pmid = 6150037 | doi = 10.1016/S0021-9258(18)89798-8 | doi-access = free }}
* {{cite journal | vauthors = Engel K, Schultz H, Martin F, Kotlyarov A, Plath K, Hahn M, Heinemann U, Gaestel M | display-authors = 6 | title = Constitutive activation of mitogen-activated protein kinase-activated protein kinase 2 by mutation of phosphorylation sites and an A-helix motif | journal = The Journal of Biological Chemistry | volume = 270 | issue = 45 | pages = 27213–21 | date = novembar 1995 | pmid = 7592979 | doi = 10.1074/jbc.270.45.27213 | doi-access = free }}
* {{cite journal | vauthors = Lavoie JN, Lambert H, Hickey E, Weber LA, Landry J | title = Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27 | journal = Molecular and Cellular Biology | volume = 15 | issue = 1 | pages = 505–16 | date = januar 1995 | pmid = 7799959 | pmc = 232001 | doi = 10.1128/MCB.15.1.505 }}
* {{cite journal | vauthors = Sutherland C, Alterio J, Campbell DG, Le Bourdellès B, Mallet J, Haavik J, Cohen P | title = Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2 | journal = European Journal of Biochemistry | volume = 217 | issue = 2 | pages = 715–22 | date = oktobar 1993 | pmid = 7901013 | doi = 10.1111/j.1432-1033.1993.tb18297.x | doi-access = free }}
* {{cite journal | vauthors = Knauf U, Jakob U, Engel K, Buchner J, Gaestel M | title = 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 | journal = The EMBO Journal | volume = 13 | issue = 1 | pages = 54–60 | date = januar 1994 | pmid = 7905823 | pmc = 394778 | doi = 10.1002/j.1460-2075.1994.tb06234.x }}
* {{cite journal | vauthors = Freshney NW, Rawlinson L, Guesdon F, Jones E, Cowley S, Hsuan J, Saklatvala J | title = Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27 | journal = Cell | volume = 78 | issue = 6 | pages = 1039–49 | date = septembar 1994 | pmid = 7923354 | doi = 10.1016/0092-8674(94)90278-X | s2cid = 37608621 }}
* {{cite journal | vauthors = Rivera VM, Miranti CK, Misra RP, Ginty DD, Chen RH, Blenis J, Greenberg ME | title = A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity | journal = Molecular and Cellular Biology | volume = 13 | issue = 10 | pages = 6260–73 | date = oktobar 1993 | pmid = 8413226 | pmc = 364685 | doi = 10.1128/mcb.13.10.6260 }}
* {{cite journal | vauthors = Beyaert R, Cuenda A, Vanden Berghe W, Plaisance S, Lee JC, Haegeman G, Cohen P, Fiers W | display-authors = 6 | title = The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor | journal = The EMBO Journal | volume = 15 | issue = 8 | pages = 1914–23 | date = april 1996 | pmid = 8617238 | pmc = 450110 | doi = 10.1002/j.1460-2075.1996.tb00542.x }}
* {{cite journal | vauthors = Ben-Levy R, Leighton IA, Doza YN, Attwood P, Morrice N, Marshall CJ, Cohen P | title = Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2 | journal = The EMBO Journal | volume = 14 | issue = 23 | pages = 5920–30 | date = decembar 1995 | pmid = 8846784 | pmc = 394711 | doi = 10.1002/j.1460-2075.1995.tb00280.x }}
* {{cite journal | vauthors = Tan Y, Rouse J, Zhang A, Cariati S, Cohen P, Comb MJ | title = FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2 | journal = The EMBO Journal | volume = 15 | issue = 17 | pages = 4629–42 | date = septembar 1996 | pmid = 8887554 | pmc = 452194 | doi = 10.1002/j.1460-2075.1996.tb00840.x }}
* {{cite journal | vauthors = Huang CK, Zhan L, Ai Y, Jongstra J | title = LSP1 is the major substrate for mitogen-activated protein kinase-activated protein kinase 2 in human neutrophils | journal = The Journal of Biological Chemistry | volume = 272 | issue = 1 | pages = 17–9 | date = januar 1997 | pmid = 8995217 | doi = 10.1074/jbc.272.1.17 | doi-access = free }}
* {{cite journal | vauthors = Krump E, Sanghera JS, Pelech SL, Furuya W, Grinstein S | title = Chemotactic peptide N-formyl-met-leu-phe activation of p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase-2 in human neutrophils | journal = The Journal of Biological Chemistry | volume = 272 | issue = 2 | pages = 937–44 | date = januar 1997 | pmid = 8995385 | doi = 10.1074/jbc.272.2.937 | doi-access = free }}
* {{cite journal | vauthors = Engel K, Kotlyarov A, Gaestel M | title = Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation | journal = The EMBO Journal | volume = 17 | issue = 12 | pages = 3363–71 | date = juni 1998 | pmid = 9628873 | pmc = 1170674 | doi = 10.1093/emboj/17.12.3363 }}
* {{cite journal | vauthors = Craxton A, Shu G, Graves JD, Saklatvala J, Krebs EG, Clark EA | title = p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes | journal = Journal of Immunology | volume = 161 | issue = 7 | pages = 3225–36 | date = oktobar 1998 | pmid = 9759836 }}
* {{cite journal | vauthors = Heidenreich O, Neininger A, Schratt G, Zinck R, Cahill MA, Engel K, Kotlyarov A, Kraft R, Kostka S, Gaestel M, Nordheim A | display-authors = 6 | title = MAPKAP kinase 2 phosphorylates serum response factor in vitro and in vivo | journal = The Journal of Biological Chemistry | volume = 274 | issue = 20 | pages = 14434–43 | date = maj 1999 | pmid = 10318869 | doi = 10.1074/jbc.274.20.14434 | doi-access = free }}
{{refend}}

==Vanjski linkovi==
{{PDB Gallery|geneid=9261}}
{{Serin/treonin-specifične protein kinaze}}
{{Enzimi}}
{{Portal|Biologija|border=no}}

[[Kategorija:Geni na hromosomu 1]]
[[Kategorija:Enzimi]]
[[Kategorija:EC 2.7.11]]
[[Kategorija:Ljudski proteini]]
[[Kategorija:Proteomika]]

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Nazad na MAPKAPK2.

Preuzeto iz "https://bs.wikipedia.org/wiki/MAPKAPK2"