P38 mitogen-activated protein kinases: Difference between revisions

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{{main|Mitogen-activated protein kinase}}
{{main|Mitogen-activated protein kinase}}
'''P38 mitogen-activated protein kinases''' are a class of [[mitogen-activated protein kinase]]s (MAPKs) that are responsive to stress stimuli, such as [[cytokines]], [[ultraviolet]] irradiation, heat shock, and [[osmotic]] shock, and are involved in cell differentiation, [[apoptosis]] and [[autophagy]]. Persistent activation of the p38 MAPK pathway in muscle [[Myosatellite cell|satellite cells]] (muscle [[stem cell]]s) due to [[ageing]], impairs muscle regeneration.<ref name="pmid27626031 ">{{cite journal | vauthors=Segalés J, Perdiguero E, Muñoz-Cánoves P | title=Regulation of Muscle Stem Cell Functions: A Focus on the p38 MAPK Signaling Pathway | journal= [[Frontiers Media|Frontiers in Cell and Developmental Biology]] | volume=4 | pages=91 | year=2016 | url=http://journal.frontiersin.org/article/10.3389/fcell.2016.00091/full | doi= 10.3389/fcell.2016.00091 | pmc = 5003838 | pmid=27626031}}</ref>
{{infobox protein
 
p38 MAP Kinase (MAPK), also called RK or CSBP (Cytokinin Specific Binding Protein), is the mammalian [[orthologue]] of the [[yeast]] [[Hog1p]] MAP kinase,<ref name="pmid7914033">{{cite journal |vauthors=Han J, Lee JD, Bibbs L, Ulevitch RJ | title = A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells | journal = Science | volume = 265 | issue = 5173 | pages = 808–11 |date=August 1994 | pmid = 7914033  | doi = 10.1126/science.7914033}}</ref> which participates in a signaling 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]].
 
{|
|{{infobox protein
| Name = [[MAPK11|mitogen-activated protein kinase 11]]
| Name = [[MAPK11|mitogen-activated protein kinase 11]]
| caption =
| caption =
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| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
|{{infobox protein
{{infobox protein
| Name = [[MAPK12|mitogen-activated protein kinase 12]]
| Name = [[MAPK12|mitogen-activated protein kinase 12]]
| caption =
| caption =
Line 46: Line 39:
| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
|-
{{infobox protein
|{{infobox protein
| Name = [[MAPK13|mitogen-activated protein kinase 13]]
| Name = [[MAPK13|mitogen-activated protein kinase 13]]
| caption =
| caption =
Line 66: Line 58:
| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
|{{infobox protein
{{infobox protein
| Name = [[MAPK14|mitogen-activated protein kinase 14]]
| Name = [[MAPK14|mitogen-activated protein kinase 14]]
| caption =
| caption =
Line 85: Line 77:
| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
|}
'''P38 mitogen-activated protein kinases''' are a class of [[mitogen-activated protein kinase]]s (MAPKs) that are responsive to stress stimuli, such as [[cytokines]], [[ultraviolet]] irradiation, heat shock, and [[osmotic]] shock, and are involved in cell differentiation, [[apoptosis]] and [[autophagy]]. Persistent activation of the p38 MAPK pathway in muscle [[Myosatellite cell|satellite cells]] (muscle [[stem cell]]s) due to [[ageing]], impairs muscle regeneration.<ref name="pmid27626031 ">{{cite journal | vauthors = Segalés J, Perdiguero E, Muñoz-Cánoves P | title = Regulation of Muscle Stem Cell Functions: A Focus on the p38 MAPK Signaling Pathway | journal = Frontiers in Cell and Developmental Biology | volume = 4 | pages = 91 | year = 2016 | pmid = 27626031 | pmc = 5003838 | doi = 10.3389/fcell.2016.00091 }}</ref>
 
p38 MAP Kinase (MAPK), also called RK or CSBP (Cytokinin Specific Binding Protein), is the mammalian [[orthologue]] of the [[yeast]] [[Hog1p]] MAP kinase,<ref name="pmid7914033">{{cite journal | vauthors = Han J, Lee JD, Bibbs L, Ulevitch RJ | title = A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells | journal = Science | volume = 265 | issue = 5173 | pages = 808–11 | date = August 1994 | pmid = 7914033 | doi = 10.1126/science.7914033 }}</ref> which participates in a signaling cascade controlling cellular responses to cytokines and stress.


[[MKK3]] and [[SEK (gene)|SEK]] activate p38 MAP kinase by [[phosphorylation]] at [[threonine|Thr]]-180 and [[tyrosine|Tyr]]-182. Activated p38 MAP kinase has been shown to phosphorylate and activate [[MAPKAPK2|MAPKAP kinase 2]] and to phosphorylate the transcription factors [[ATF2]], [[Mac (gene)|Mac]] and [[MEF2]]. p38 also has been shown to phosphorylate post-transcriptional regulating factors like [[ZFP36|TTP]].<ref name="pmid19416727">{{cite journal |vauthors=Tudor C, Marchese FP, Hitti E, Aubareda A, Rawlinson L, Gaestel M, Blackshear PJ, Clark AR, Saklatvala J, Dean JL | title = The p38 MAPK pathway inhibits tristetraprolin-directed decay of interleukin-10 and pro-inflammatory mediator mRNAs in murine macrophages | journal = FEBS Lett. | volume = 583 | issue = 12 | pages = 1933–8 |date=June 2009 | pmid = 19416727  | doi = 10.1016/j.febslet.2009.04.039 }}</ref>
Four p38 MAP kinases, p38-α ([[MAPK14]]), -β ([[MAPK11]]), -γ ([[MAPK12]] / ERK6), and -δ ([[MAPK13]] / SAPK4), have been identified. Similar to the [[C-Jun N-terminal kinases|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]].


==Pathology associated with dysregulation of P38 enzymatic activity==
[[MKK3]] and [[SEK (gene)|SEK]] activate p38 MAP kinase by [[phosphorylation]] at [[threonine|Thr]]-180 and [[tyrosine|Tyr]]-182. Activated p38 MAP kinase has been shown to phosphorylate and activate [[MAPKAPK2|MAPKAP kinase 2]] and to phosphorylate the transcription factors [[ATF2]], [[Mac (gene)|Mac]] and [[MEF2]]. p38 also has been shown to phosphorylate post-transcriptional regulating factors like [[ZFP36|TTP]].<ref name="pmid19416727">{{cite journal | vauthors = Tudor C, Marchese FP, Hitti E, Aubareda A, Rawlinson L, Gaestel M, Blackshear PJ, Clark AR, Saklatvala J, Dean JL | title = The p38 MAPK pathway inhibits tristetraprolin-directed decay of interleukin-10 and pro-inflammatory mediator mRNAs in murine macrophages | journal = FEBS Letters | volume = 583 | issue = 12 | pages = 1933–8 | date = June 2009 | pmid = 19416727 | pmc = 4798241 | doi = 10.1016/j.febslet.2009.04.039 }}</ref>
Abnormal activity (higher or lower than physiological) of P38 has been implicated in pathological events in several tissues,  that  include  neuronal  <ref>{{cite journal | last1 = Yan | first1 = SD | title = RAGE and Alzheimer's disease: a progression factor for amyloid-beta-induced cellular perturbation? | journal = J Alzheimers Dis. | date = 2009 | pmid = 19387116 | doi = 10.3233/JAD-2009-1030 | volume = 16 | pages = 833–843}}</ref><ref>{{cite journal | last1 = Bachstetter | first1 = AD | title = Microglial p38α MAPK is a key regulator of proinflammatory cytokine up-regulation induced by toll-like receptor (TLR) ligands or beta-amyloid (Aβ). | journal = J Neuroinflammation | date = 2011 | pmid = 21733175 | doi = 10.1186/1742-2094-8-79 | volume = 8 | pages = 79}}</ref><ref>{{cite journal | last1 = Zhou | first1 = Z | title = Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes. | journal = J Neuroinflammation | date = 2017 | pmid = 28381303 | doi = 10.1186/s12974-017-0845-2 | volume = 14 | pages = 75}}</ref>
bone,<ref>{{cite journal | last1 = Wei | first1 = S | last2 = Siegal | first2 = GP | title = Mechanisms modulating inflammatory osteolysis: a review with insights into therapeutic targets. | journal = Pathol Res Pract. | date = 2008 | pmid = 18757139 | doi = 10.1016/j.prp.2008.07.002 | volume = 204 | pages = 695–706}}</ref>  lung <ref>{{cite journal | last1 = Barnes | first1 =  PJ | title = Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease. | journal = Pharmacol. Rev. | date = 2016 | pmid = 27363440 | doi = 10.1124/pr.116.012518 | volume = 68 | pages = 788–815}}</ref>  cardiac and skeletal muscle,<ref>{{cite journal | last1 = Wang | first1 = S | title = The Role of p38 MAPK in the Development of Diabetic Cardiomyopathy. | journal = Int J Mol Sci. | date = 2016 | pmid = 27376265 | doi = 10.3390/ijms17071037 | volume = 17 | pages = E1037 }}</ref><ref>{{cite journal | last1 = Segalés | first1 = J | title = Regulation of Muscle Stem Cell Functions: A Focus on the p38 MAPK Signaling Pathway. | journal = Front Cell Dev Biol | date = August 2016 | pmid = 27626031 | doi = 10.3389/fcell.2016.00091 | volume = 4 | pages = 91 }}</ref>    red blood cells,<ref>{{cite journal | last1 = Lang | first1 = E | title = Suicidal death of erythrocytes in cancer and its chemotherapy: A potential target in the treatment of tumor-associated anemia. | journal = Int J Cancer | date = Oct 2017 | pmid = 28542880  | doi =  10.1002/ijc.30800 | volume = 141 | pages = 1522–1528 }}</ref> and fetal tissues.<ref>{{cite journal | last1 = Bonney | first1 = EA | title = Mapping out p38MAPK. | journal = Am J Reprod Immunol. | date = 2017 | pmid = 28194826 | doi = 10.1111/aji.12652 | volume = 77 | issue = 5}}</ref> The protein product of Proto-oncogene RAS can increase activity of p38, and thereby cause excessively high activity of transcription factor NF-κB. This transcription factor is normally regulated from intracellular pathways that integrate signals from the surrounding tissue and the immune system. In turn these signals coordinate between cell survival and cell death. Dysregulated NF-κB activity can activate genes that cause cancer cell survival, and can also activate genes that facilitate cancer cell metastasis to other tissues.<ref>{{cite journal | last1 = Vlahopoulos | first1 = SA | title = Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode. | journal = Cancer biology & medicine | date = August 2017 | pmid = 28884042 | doi = 10.20892/j.issn.2095-3941.2017.0029 | volume = 14 | pages = 254–270 | pmc = 5570602}}</ref>


==P38 inhibitors==
== Clinical significance ==
P38 inhibitors are being sought for possible therapeutic effect on autoimmune diseases and inflammatory processes,<ref name="pmid16178744">{{cite journal |vauthors=Goldstein DM, Gabriel T | title = Pathway to the clinic: inhibition of P38 MAP kinase. A review of ten chemotypes selected for development | journal = Current topics in medicinal chemistry| volume = 5 | issue = 10 | pages = 1017–29 | year = 2005 | pmid = 16178744 | doi = 10.2174/1568026054985939}}</ref> e.g. [[pamapimod]].<ref name="pmid18776065">{{cite journal |vauthors=Hill RJ, Dabbagh K, Phippard D, Li C, Suttmann RT, Welch M, Papp E, Song KW, Chang KC, Leaffer D, Kim YN, Roberts RT, Zabka TS, Aud D, Dal Porto J, Manning AM, Peng SL, Goldstein DM, Wong BR | title = Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity | journal = J. Pharmacol. Exp. Ther. | volume = 327 | issue = 3 | pages = 610–9 |date=December 2008 | pmid = 18776065 | doi = 10.1124/jpet.108.139006 }}</ref> Some have started clinical trials, e.g. [[PH-797804]] for [[chronic obstructive pulmonary disease|COPD]].<ref>{{cite web |url=http://www.docguide.com/novel-p38-inhibitor-shows-promise-anti-inflammatory-treatment-patients-copd |title=Novel p38 Inhibitor Shows Promise as Anti-Inflammatory Treatment for Patients With COPD |year=2010 }}</ref> Other p38 inhibitors include BIRB 796, VX-702, SB239063, SB202190, SB203580, SCIO 469, and BMS 582949.
Abnormal activity (higher or lower than physiological) of P38 has been implicated in pathological events in several tissues, that  include  neuronal  <ref>{{cite journal | vauthors = Yan SD, Bierhaus A, Nawroth PP, Stern DM | title = RAGE and Alzheimer's disease: a progression factor for amyloid-beta-induced cellular perturbation? | journal = Journal of Alzheimer's Disease | volume = 16 | issue = 4 | pages = 833–43 | date = 2009 | pmid = 19387116 | pmc = 3726270 | doi = 10.3233/JAD-2009-1030 }}</ref><ref>{{cite journal | vauthors = Bachstetter AD, Xing B, de Almeida L, Dimayuga ER, Watterson DM, Van Eldik LJ | title = Microglial p38α MAPK is a key regulator of proinflammatory cytokine up-regulation induced by toll-like receptor (TLR) ligands or beta-amyloid (Aβ) | journal = Journal of Neuroinflammation | volume = 8 | pages = 79 | date = July 2011 | pmid = 21733175 | pmc = 3142505 | doi = 10.1186/1742-2094-8-79 }}</ref><ref>{{cite journal | vauthors = Zhou Z, Bachstetter AD, Späni CB, Roy SM, Watterson DM, Van Eldik LJ | title = Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes | journal = Journal of Neuroinflammation | volume = 14 | issue = 1 | pages = 75 | date = April 2017 | pmid = 28381303 | pmc = 5382362 | doi = 10.1186/s12974-017-0845-2 }}</ref>
bone,<ref>{{cite journal | vauthors = Wei S, Siegal GP | title = Mechanisms modulating inflammatory osteolysis: a review with insights into therapeutic targets | journal = Pathology, Research and Practice | volume = 204 | issue = 10 | pages = 695–706 | date = 2008 | pmid = 18757139 | pmc = 3747958 | doi = 10.1016/j.prp.2008.07.002 }}</ref>  lung <ref>{{cite journal | vauthors = Barnes PJ | title = Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease | journal = Pharmacological Reviews | volume = 68 | issue = 3 | pages = 788–815 | date = July 2016 | pmid = 27363440 | doi = 10.1124/pr.116.012518 }}</ref> cardiac and skeletal muscle,<ref>{{cite journal | vauthors = Wang S, Ding L, Ji H, Xu Z, Liu Q, Zheng Y | title = The Role of p38 MAPK in the Development of Diabetic Cardiomyopathy | journal = International Journal of Molecular Sciences | volume = 17 | issue = 7 | pages = E1037 | date = June 2016 | pmid = 27376265 | pmc = 4964413 | doi = 10.3390/ijms17071037 }}</ref><ref>{{cite journal | vauthors = Segalés J, Perdiguero E, Muñoz-Cánoves P | title = Regulation of Muscle Stem Cell Functions: A Focus on the p38 MAPK Signaling Pathway | journal = Frontiers in Cell and Developmental Biology | volume = 4 | pages = 91 | date = August 2016 | pmid = 27626031 | pmc = 5003838 | doi = 10.3389/fcell.2016.00091 }}</ref>    red blood cells,<ref>{{cite journal | vauthors = Lang E, Bissinger R, Qadri SM, Lang F | title = Suicidal death of erythrocytes in cancer and its chemotherapy: A potential target in the treatment of tumor-associated anemia | journal = International Journal of Cancer | volume = 141 | issue = 8 | pages = 1522–1528 | date = October 2017 | pmid = 28542880 | doi = 10.1002/ijc.30800 }}</ref> and fetal tissues.<ref>{{cite journal | vauthors = Bonney EA | title = Mapping out p38MAPK | journal = American Journal of Reproductive Immunology | volume = 77 | issue = 5 | date = May 2017 | pmid = 28194826 | pmc = 5527295 | doi = 10.1111/aji.12652 }}</ref> The protein product of Proto-oncogene RAS can increase activity of p38, and thereby cause excessively high activity of transcription factor NF-κB. This transcription factor is normally regulated from intracellular pathways that integrate signals from the surrounding tissue and the immune system. In turn these signals coordinate between cell survival and cell death. Dysregulated NF-κB activity can activate genes that cause cancer cell survival, and can also activate genes that facilitate cancer cell metastasis to other tissues.<ref>{{cite journal | vauthors = Vlahopoulos SA | title = Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode | journal = Cancer Biology & Medicine | volume = 14 | issue = 3 | pages = 254–270 | date = August 2017 | pmid = 28884042 | pmc = 5570602 | doi = 10.20892/j.issn.2095-3941.2017.0029 }}</ref>


==References==
== Inhibitors ==
P38 inhibitors are being sought for possible therapeutic effect on autoimmune diseases and inflammatory processes,<ref name="pmid16178744">{{cite journal | vauthors = Goldstein DM, Gabriel T | title = Pathway to the clinic: inhibition of P38 MAP kinase. A review of ten chemotypes selected for development | journal = Current Topics in Medicinal Chemistry | volume = 5 | issue = 10 | pages = 1017–29 | year = 2005 | pmid = 16178744 | doi = 10.2174/1568026054985939 }}</ref> e.g. [[pamapimod]].<ref name="pmid18776065">{{cite journal | vauthors = Hill RJ, Dabbagh K, Phippard D, Li C, Suttmann RT, Welch M, Papp E, Song KW, Chang KC, Leaffer D, Kim YN, Roberts RT, Zabka TS, Aud D, Dal Porto J, Manning AM, Peng SL, Goldstein DM, Wong BR | title = Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 327 | issue = 3 | pages = 610–9 | date = December 2008 | pmid = 18776065 | doi = 10.1124/jpet.108.139006 }}</ref> Some have started clinical trials, e.g. [[PH-797804]] for [[chronic obstructive pulmonary disease|COPD]].<ref>{{cite web |url=http://www.docguide.com/novel-p38-inhibitor-shows-promise-anti-inflammatory-treatment-patients-copd |title=Novel p38 Inhibitor Shows Promise as Anti-Inflammatory Treatment for Patients With COPD |year=2010 }}</ref>  Other p38 inhibitors include BIRB 796, VX-702, SB239063, SB202190, SB203580, SCIO 469, and BMS 582949.
 
== References ==
{{Reflist}}
{{Reflist}}


==External links==
== External links ==
* {{MeshName|p38+Mitogen-Activated+Protein+Kinases}}
* {{MeshName|p38+Mitogen-Activated+Protein+Kinases}}
* [http://www.biocarta.com/pathfiles/m_p38mapkPathway.asp P38mapkPathway]
* [http://www.biocarta.com/pathfiles/m_p38mapkPathway.asp P38mapkPathway]
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[[Category:EC 2.7.11]]
[[Category:EC 2.7.11]]
[[Category:Protein kinases]]
[[Category:Protein kinases]]


{{2.7-enzyme-stub}}
{{2.7-enzyme-stub}}

Latest revision as of 12:20, 9 January 2019

Main article: Mitogen-activated protein kinase
mitogen-activated protein kinase 11
Identifiers
SymbolMAPK11
Alt. symbolsPRKM11
Entrez5600
HUGO6873
OMIM602898
RefSeqNM_002751
UniProtQ15759
Other data
EC number2.7.11.24
LocusChr. 22 q13.33
mitogen-activated protein kinase 12
Identifiers
SymbolMAPK12
Alt. symbolsSAPK3
Entrez6300
HUGO6874
OMIM602399
RefSeqNM_002969
UniProtP53778
Other data
EC number2.7.11.24
LocusChr. 22 q13.3
mitogen-activated protein kinase 13
Identifiers
SymbolMAPK13
Alt. symbolsPRKM13
Entrez5603
HUGO6875
OMIM602899
RefSeqNM_002754
UniProtO15264
Other data
EC number2.7.11.24
LocusChr. 6 p21
mitogen-activated protein kinase 14
Identifiers
SymbolMAPK14
Alt. symbolsCSPB1, CSBP1, CSBP2
Entrez1432
HUGO6876
OMIM600289
RefSeqNM_001315
UniProtQ16539
Other data
EC number2.7.11.24
LocusChr. 6 p21.3-21.2

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 differentiation, apoptosis and autophagy. Persistent activation of the p38 MAPK pathway in muscle satellite cells (muscle stem cells) due to ageing, impairs muscle regeneration.[1]

p38 MAP Kinase (MAPK), also called RK or CSBP (Cytokinin Specific Binding Protein), is the mammalian orthologue of the yeast Hog1p MAP kinase,[2] which participates in a signaling 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.[3]

Clinical significance

Abnormal activity (higher or lower than physiological) of P38 has been implicated in pathological events in several tissues, that include neuronal [4][5][6] bone,[7] lung [8] cardiac and skeletal muscle,[9][10] red blood cells,[11] and fetal tissues.[12] The protein product of Proto-oncogene RAS can increase activity of p38, and thereby cause excessively high activity of transcription factor NF-κB. This transcription factor is normally regulated from intracellular pathways that integrate signals from the surrounding tissue and the immune system. In turn these signals coordinate between cell survival and cell death. Dysregulated NF-κB activity can activate genes that cause cancer cell survival, and can also activate genes that facilitate cancer cell metastasis to other tissues.[13]

Inhibitors

P38 inhibitors are being sought for possible therapeutic effect on autoimmune diseases and inflammatory processes,[14] e.g. pamapimod.[15] Some have started clinical trials, e.g. PH-797804 for COPD.[16] Other p38 inhibitors include BIRB 796, VX-702, SB239063, SB202190, SB203580, SCIO 469, and BMS 582949.

References

  1. ↑ Segalés J, Perdiguero E, Muñoz-Cánoves P (2016). "Regulation of Muscle Stem Cell Functions: A Focus on the p38 MAPK Signaling Pathway". Frontiers in Cell and Developmental Biology. 4: 91. doi:10.3389/fcell.2016.00091. PMC 5003838. PMID 27626031.
  2. ↑ Han J, Lee JD, Bibbs L, Ulevitch RJ (August 1994). "A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells". Science. 265 (5173): 808–11. doi:10.1126/science.7914033. PMID 7914033.
  3. ↑ Tudor C, Marchese FP, Hitti E, Aubareda A, Rawlinson L, Gaestel M, Blackshear PJ, Clark AR, Saklatvala J, Dean JL (June 2009). "The p38 MAPK pathway inhibits tristetraprolin-directed decay of interleukin-10 and pro-inflammatory mediator mRNAs in murine macrophages". FEBS Letters. 583 (12): 1933–8. doi:10.1016/j.febslet.2009.04.039. PMC 4798241. PMID 19416727.
  4. ↑ Yan SD, Bierhaus A, Nawroth PP, Stern DM (2009). "RAGE and Alzheimer's disease: a progression factor for amyloid-beta-induced cellular perturbation?". Journal of Alzheimer's Disease. 16 (4): 833–43. doi:10.3233/JAD-2009-1030. PMC 3726270. PMID 19387116.
  5. ↑ Bachstetter AD, Xing B, de Almeida L, Dimayuga ER, Watterson DM, Van Eldik LJ (July 2011). "Microglial p38α MAPK is a key regulator of proinflammatory cytokine up-regulation induced by toll-like receptor (TLR) ligands or beta-amyloid (Aβ)". Journal of Neuroinflammation. 8: 79. doi:10.1186/1742-2094-8-79. PMC 3142505. PMID 21733175.
  6. ↑ Zhou Z, Bachstetter AD, Späni CB, Roy SM, Watterson DM, Van Eldik LJ (April 2017). "Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes". Journal of Neuroinflammation. 14 (1): 75. doi:10.1186/s12974-017-0845-2. PMC 5382362. PMID 28381303.
  7. ↑ Wei S, Siegal GP (2008). "Mechanisms modulating inflammatory osteolysis: a review with insights into therapeutic targets". Pathology, Research and Practice. 204 (10): 695–706. doi:10.1016/j.prp.2008.07.002. PMC 3747958. PMID 18757139.
  8. ↑ Barnes PJ (July 2016). "Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease". Pharmacological Reviews. 68 (3): 788–815. doi:10.1124/pr.116.012518. PMID 27363440.
  9. ↑ Wang S, Ding L, Ji H, Xu Z, Liu Q, Zheng Y (June 2016). "The Role of p38 MAPK in the Development of Diabetic Cardiomyopathy". International Journal of Molecular Sciences. 17 (7): E1037. doi:10.3390/ijms17071037. PMC 4964413. PMID 27376265.
  10. ↑ Segalés J, Perdiguero E, Muñoz-Cánoves P (August 2016). "Regulation of Muscle Stem Cell Functions: A Focus on the p38 MAPK Signaling Pathway". Frontiers in Cell and Developmental Biology. 4: 91. doi:10.3389/fcell.2016.00091. PMC 5003838. PMID 27626031.
  11. ↑ Lang E, Bissinger R, Qadri SM, Lang F (October 2017). "Suicidal death of erythrocytes in cancer and its chemotherapy: A potential target in the treatment of tumor-associated anemia". International Journal of Cancer. 141 (8): 1522–1528. doi:10.1002/ijc.30800. PMID 28542880.
  12. ↑ Bonney EA (May 2017). "Mapping out p38MAPK". American Journal of Reproductive Immunology. 77 (5). doi:10.1111/aji.12652. PMC 5527295. PMID 28194826.
  13. ↑ Vlahopoulos SA (August 2017). "Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode". Cancer Biology & Medicine. 14 (3): 254–270. doi:10.20892/j.issn.2095-3941.2017.0029. PMC 5570602. PMID 28884042.
  14. ↑ Goldstein DM, Gabriel T (2005). "Pathway to the clinic: inhibition of P38 MAP kinase. A review of ten chemotypes selected for development". Current Topics in Medicinal Chemistry. 5 (10): 1017–29. doi:10.2174/1568026054985939. PMID 16178744.
  15. ↑ Hill RJ, Dabbagh K, Phippard D, Li C, Suttmann RT, Welch M, Papp E, Song KW, Chang KC, Leaffer D, Kim YN, Roberts RT, Zabka TS, Aud D, Dal Porto J, Manning AM, Peng SL, Goldstein DM, Wong BR (December 2008). "Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity". The Journal of Pharmacology and Experimental Therapeutics. 327 (3): 610–9. doi:10.1124/jpet.108.139006. PMID 18776065.
  16. ↑ "Novel p38 Inhibitor Shows Promise as Anti-Inflammatory Treatment for Patients With COPD". 2010.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=P38_mitogen-activated_protein_kinases&oldid=1518735"