P38 mitogen-activated protein kinases
Encyclopedia
P38 mitogen-activated protein kinases are a class of mitogen-activated protein kinase
s that are responsive to stress stimuli, such as cytokines, ultraviolet
irradiation, heat shock, and osmotic shock, and are involved in cell differentiation and apoptosis
.
p38 MAP Kinase (MAPK), also called RK or CSBP, is the mammalian orthologue of the yeast
Hog1p MAP kinase, which participates in a signalling cascade controlling cellular responses to cytokines and stress.
Four p38 MAP kinases, p38-α (MAPK14
), -β (MAPK11
), -γ (MAPK12
/ ERK6), and -δ (MAPK13
/ SAPK4), have been identified. Similar to the SAPK/JNK pathway, p38 MAP kinase is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharides (LPS), Ultraviolet
light, and growth factors.
MKK3 and SEK
activate p38 MAP kinase by phosphorylation
at Thr
-180 and Tyr
-182. Activated p38 MAP kinase has been shown to phosphorylate and activate MAPKAP kinase 2
and to phosphorylate the transcription factors ATF2, Mac
and MEF2
. p38 also has been shown to phosphorylate post-transcriptional regulating factors like TTP
.
.
Mitogen-activated protein kinase
Mitogen-activated protein kinases are serine/threonine-specific protein kinases that respond to extracellular stimuli and regulate various cellular activities, such as gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.-Activation:MAP kinases are activated...
s that are responsive to stress stimuli, such as cytokines, ultraviolet
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
irradiation, heat shock, and osmotic shock, and are involved in cell differentiation and apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
.
p38 MAP Kinase (MAPK), also called RK or CSBP, is the mammalian orthologue of the yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
Hog1p MAP kinase, which participates in a signalling cascade controlling cellular responses to cytokines and stress.
Four p38 MAP kinases, p38-α (MAPK14
MAPK14
Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.-Interactions:MAPK14 has been shown to interact with Casein kinase 2, alpha 1, RPS6KA4, MAPKAPK2, CDC25B, DUSP1, ZFP36L1, CDC25C, MAPKAPK3, Activating transcription factor 2, MAPK1,...
), -β (MAPK11
MAPK11
Mitogen-activated protein kinase 11 is an enzyme that in humans is encoded by the MAPK11 gene.-Interactions:MAPK11 has been shown to interact with HDAC3 and Promyelocytic leukemia protein.-Further reading:...
), -γ (MAPK12
MAPK12
Mitogen-activated protein kinase 12 , also known as extracellular signal-regulated kinase 6 or stress-activated protein kinase 3 , is an enzyme that in humans is encoded by the MAPK12 gene.- Function :...
/ ERK6), and -δ (MAPK13
MAPK13
Mitogen-activated protein kinase 13 , also known as stress-activated protein kinase 4 , is an enzyme that in humans is encoded by the MAPK13 gene.- Function :The protein encoded by this gene is a member of the MAP kinase family...
/ SAPK4), have been identified. Similar to the SAPK/JNK pathway, p38 MAP kinase is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharides (LPS), Ultraviolet
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
light, and growth factors.
MKK3 and SEK
SEK
SEK may stand for:*Swedish krona, the currency of Sweden*Federation of Swiss Protestant Churches *SEK Studio, a North Korean animation studio* Stagecoach in East Kent...
activate p38 MAP kinase by phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
at Thr
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
-180 and Tyr
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
-182. Activated p38 MAP kinase has been shown to phosphorylate and activate MAPKAP kinase 2
MAPKAPK2
MAP kinase-activated protein kinase 2 is an enzyme that in humans is encoded by the MAPKAPK2 gene.-Interactions:MAPKAPK2 has been shown to interact with MAPK14, AKT1, PHC2 and SHC1.-Further reading:...
and to phosphorylate the transcription factors ATF2, Mac
MAC
-Aviation:* Martin's Air Charter, now Martinair* Mean Aerodynamic Chord* Merchant aircraft carrier, used during World War II by Britain and the Netherlands.* Metropolitan Airports Commission, the operator of airports in the Minneapolis-St...
and MEF2
Mef2
In the field of molecular biology, myocyte enhancer factor-2 proteins are a family of transcription factors which through control of gene expression are important regulators of cellular differentiation and consequently play a critical role in embryonic development. In adult organisms, Mef2...
. p38 also has been shown to phosphorylate post-transcriptional regulating factors like TTP
ZFP36
Tristetraprolin also known as zinc finger protein 36 homolog is a protein that in humans is encoded by the ZFP36 gene....
.
P38 inhibitors
P38 inhibitors are being sought for possible therapeutic effect on autoimmune diseases and inflammatory processes, e.g. pamapimod. Some have started clinical trials, e.g. PH-797804 for COPDChronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
.