MAPKAPK2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMAPKAPK2, MAPKAP-K2, MK-2, MK2, mitogen-activated protein kinase-activated protein kinase 2, MAPK activated protein kinase 2
External IDsOMIM: 602006 MGI: 109298 HomoloGene: 56412 GeneCards: MAPKAPK2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004759
NM_032960

NM_008551

RefSeq (protein)

NP_004750
NP_116584

NP_032577

Location (UCSC)Chr 1: 206.68 – 206.73 MbChr 1: 130.98 – 131.03 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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]

See also

Interactions

MAPKAPK2 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000162889 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000016528 - Ensembl, May 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.
  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.
  6. ^ Stokoe D, Caudwell B, Cohen PT, Cohen P (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.
  7. ^ a b c 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.
  8. ^ "Entrez Gene: MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2".
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ Yessenkyzy A, Saliev T, Zhanaliyeva M, Masoud AR, Umbayev B, Sergazy S, 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, 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.
  16. ^ 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.
  17. ^ a b Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ Dondelinger Y, Delanghe T, Rojas-Rivera D, Priem D, Delvaeye T, Bruggeman I, 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.

Further reading