MAP kinase-activated protein kinase 2 is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that in humans is encoded by the ''MAPKAPK2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
This gene encodes a member of the
Ser/Thr protein kinase family. This kinase is regulated through direct phosphorylation by
p38 MAP kinase
p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell different ...
. 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
Heat shock protein 27 (Hsp27) also known as heat shock protein beta-1 (HSPB1) is a protein that in humans is encoded by the ''HSPB1'' gene.
Hsp27 is a chaperone of the sHsp (small heat shock protein) group among α-crystallin, Hsp20, and others. ...
was shown to be its major direct substrate in vivo. Two transcript variants encoding two different isoforms have been found for this gene.
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 and vimentin remodeling. Activation of MK2 via its phosphorylation by p38 has been shown to restore the vascular barrier
and repair vascular leak, associated with over 60 medical conditions, including Acute Respiratory Distress Syndrome (
ARDS
Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin color ...
), a major cause of death around the world.
SASP initiation
MAPKAPK2 mediates the initiation of the
senescence-associated secretory phenotype
Senescence-associated secretory phenotype (SASP) is a phenotype associated with senescent cells wherein those cells secrete high levels of inflammatory cytokines, immune modulators, growth factors, and proteases. SASP may also consist of exosomes ...
(SASP) by
mTOR
The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MT ...
(mechanistic target of rapamycin).
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
Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the ...
with NF-κB.
Translation of
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
for IL1A is highly dependent upon mTOR activity.
mTOR activity increases levels of IL1A, mediated by MAPKAPK2.
See also
*
SB 203580, suppresses the activation of MAPKAPK2
*MK2-AP directly activates MAPKAPK2 independent of p38.
Interactions
MAPKAPK2 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
AKT1
RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT1'' gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) protein domains. It ...
,
[
* ]MAPK14
Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the ''MAPK14'' gene.
MAPK14 encodes p38α mitogen-activated protein kinase (MAPK) which is the prototypic member of the p38 MAPK family. p38 MAPKs ...
,
* PHC2
Polyhomeotic-like protein 2 is a protein that in humans is encoded by the ''PHC2'' gene.
Function
In Drosophila melanogaster, the 'Polycomb' group (PcG) of genes are part of a cellular memory system that is responsible for the stable inheritan ...
, and
* SHC1
SHC-transforming protein 1 is a protein that in humans is encoded by the ''SHC1'' gene. SHC has been found to be important in the regulation of apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of pro ...
.[
* ]RIPK1
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival p ...
References
Further reading
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EC 2.7.11
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