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 Interleukin-1 alpha (IL-1 alpha) also known as hematopoietin 1 is a cytokine of the interleukin 1 family that in humans is encoded by the ''IL1A'' gene. In general, Interleukin 1 is responsible for the production of inflammation, as well as the p ...

(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.

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 i ...

, *

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 and drug resistance in mammalian cells. SCOP classifies the 3D structure as belonging to th ...

. *

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 ...

Function

Vascular barrier

SASP initiation

See also

Interactions

References

Further reading