MAPKAPK2

Last updated
MAPKAPK2
Protein MAPKAPK2 PDB 1kwp.png
Available structures
PDB Ortholog search: PDBe RCSB
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
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 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]

See also

Interactions

MAPKAPK2 has been shown to interact with:

Related Research Articles

A mitogen-activated protein kinase is a type of protein kinase that is specific to the amino acids serine and threonine. MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis.

<span class="mw-page-title-main">ASK1</span> Protein-coding gene in the species Homo sapiens

Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, rheumatoid arthritis, cardiovascular and neurodegenerative diseases.

<span class="mw-page-title-main">MAPK14</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.

<span class="mw-page-title-main">MAPK7</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene.

<span class="mw-page-title-main">MAP2K6</span> Protein-coding gene in the species Homo sapiens

Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 or MAPK/ERK kinase 6 is an enzyme that in humans is encoded by the MAP2K6 gene, on chromosome 17.

<span class="mw-page-title-main">MAP2K3</span> Protein-coding gene in the species Homo sapiens

Dual specificity mitogen-activated protein kinase kinase 3 is an enzyme that in humans is encoded by the MAP2K3 gene.

<span class="mw-page-title-main">RPS6KA1</span> Enzyme

Ribosomal protein S6 kinase alpha-1 is an enzyme that in humans is encoded by the RPS6KA1 gene.

<span class="mw-page-title-main">RPS6KA3</span> Enzyme found in humans

protein S6 kinase, 90kDa, polypeptide 3, also s RPS6KA3, is an enzyme that in humans is encoded by the RPS6KA3 gene.

<span class="mw-page-title-main">MAP3K1</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene.

<span class="mw-page-title-main">MAP2K7</span> Protein-coding gene in the species Homo sapiens

Dual specificity mitogen-activated protein kinase kinase 7, also known as MAP kinase kinase 7 or MKK7, is an enzyme that in humans is encoded by the MAP2K7 gene. This protein is a member of the mitogen-activated protein kinase kinase family. The MKK7 protein exists as six different isoforms with three possible N-termini and two possible C-termini.

<span class="mw-page-title-main">RPS6KA5</span> Enzyme

Ribosomal protein S6 kinase alpha-5 is an enzyme that in humans is encoded by the RPS6KA5 gene. This kinase, together with RPS6KA4, are thought to mediate the phosphorylation of histone H3, linked to the expression of immediate early genes.

<span class="mw-page-title-main">RPS6KA2</span> Enzyme found in humans

Ribosomal protein S6 kinase alpha-2 is an enzyme that in humans is encoded by the RPS6KA2 gene.

<span class="mw-page-title-main">MAP3K4</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 4 is an enzyme that in humans is encoded by the MAP3K4 gene.

<span class="mw-page-title-main">MAP3K2</span> Protein-coding gene in the species Homo sapiens

Mitogen-Activated Protein Kinase Kinase Kinase 2 also known as MEKK2 is an enzyme that in humans is encoded by the MAP3K2 gene.

<span class="mw-page-title-main">MAPK6</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 6 is an enzyme that in humans is encoded by the MAPK6 gene.

<span class="mw-page-title-main">MAPKAPK3</span> Protein-coding gene in the species Homo sapiens

MAP kinase-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPKAPK3 gene.

<span class="mw-page-title-main">RPS6KA4</span> Enzyme found in humans

Ribosomal protein S6 kinase alpha-4 is an enzyme that in humans is encoded by the RPS6KA4 gene.

<span class="mw-page-title-main">MAPKAPK5</span>

MAP kinase-activated protein kinase 5 is an enzyme that in humans is encoded by the MAPKAPK5 gene. The protein encoded by this gene is a member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases, including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. In vitro, this kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately-spliced transcript variants of this gene encoding distinct isoforms have been reported.

<span class="mw-page-title-main">MAPK11</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 11 is an enzyme that in humans is encoded by the MAPK11 gene.

<span class="mw-page-title-main">MAPK phosphatase</span>

MAPK phosphatases (MKPs) are the largest class of phosphatases involved in down-regulating Mitogen-activated protein kinases (MAPK) signaling. MAPK signalling pathways regulate multiple features of development and homeostasis. This can involve gene regulation, cell proliferation, programmed cell death and stress responses. MAPK phosphatases are therefore important regulator components of these pathways.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000162889 - Ensembl, May 2017
  2. 1 2 3 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, 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.
  6. 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.
  7. 1 2 3 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.
  8. "Entrez Gene: MAPKAPK2 mitogen-activated protein kinase-activated protein kinase 2".
  9. 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.
  10. 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.
  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, 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, 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.
  14. 1 2 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.
  15. 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.
  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. 1 2 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.
  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. 1 2 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.
  20. 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.

Further reading