p38 mitogen-activated protein kinases

Main article: Mitogen-activated protein kinase

P38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases 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,^[1] 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.

mitogen-activated protein kinase 11 Identifiers Symbol MAPK11 Alt. symbols PRKM11 Entrez 5600 HUGO 6873 OMIM 602898 RefSeq NM_002751 UniProt Q15759 Other data EC number 2.7.11.24 Locus Chr. 22 q13.33

mitogen-activated protein kinase 12 Identifiers Symbol MAPK12 Alt. symbols SAPK3 Entrez 6300 HUGO 6874 OMIM 602399 RefSeq NM_002969 UniProt P53778 Other data EC number 2.7.11.24 Locus Chr. 22 q13.3

mitogen-activated protein kinase 13 Identifiers Symbol MAPK13 Alt. symbols PRKM13 Entrez 5603 HUGO 6875 OMIM 602899 RefSeq NM_002754 UniProt O15264 Other data EC number 2.7.11.24 Locus Chr. 6 p21

mitogen-activated protein kinase 14 Identifiers Symbol MAPK14 Alt. symbols CSPB1, CSBP1, CSBP2 Entrez 1432 HUGO 6876 OMIM 600289 RefSeq NM_001315 UniProt Q16539 Other data EC number 2.7.11.24 Locus Chr. 6 p21.3-21.2

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^{[disambiguation needed ]} and MEF2. p38 also has been shown to phosphorylate post-transcriptional regulating factors like TTP.^[2]

P38 inhibitors

P38 inhibitors are being sought for possible therapeutic effect on autoimmune diseases and inflammatory processes,^[3] e.g. pamapimod.^[4] Some have started clinical trials, e.g. PH-797804 for COPD.^[5]

References

1. ^ 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. 
2. ^ 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 Lett. 583 (12): 1933–8. doi:10.1016/j.febslet.2009.04.039. PMID 19416727. 
3. ^ Goldstein DM, Gabriel T (2005). Pathway to the clinic: inhibition of P38 MAP kinase. A review of ten chemotypes selected for development. 5. pp. 1017–29. PMID 16178744. 
4. ^ 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". J. Pharmacol. Exp. Ther. 327 (3): 610–9. doi:10.1124/jpet.108.139006. PMID 18776065. 
5. ^ "Novel p38 Inhibitor Shows Promise as Anti-Inflammatory Treatment for Patients With COPD". 2010. http://www.docguide.com/novel-p38-inhibitor-shows-promise-anti-inflammatory-treatment-patients-copd. 

External links

• MeSH p38+Mitogen-Activated+Protein+Kinases
• P38mapkPathway
• p38 Signaling Pathway
• MAP Kinase Resource

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)
Polo kinase (EC 2.7.11.21) PLK1, PLK2, PLK3, PLK4 Cyclin-dependent kinase (EC 2.7.11.22) CDK1, CDK2, CDKL2, CDK3, CDK4, CDK5, CDKL5, CDK6, CDK7, CDK8, CDK9, CDK10, CDC2L5, CRKRS, PCTK1, PCTK2, PCTK3, PFTK1, CDC2L1 (RNA-polymerase)-subunit kinase (EC 2.7.11.23) RPS6KA5, RPS6KA4, P70S6 kinase, P70-S6 Kinase 1, RPS6KB2, RPS6KA2, RPS6KA3, RPS6KA1, RPS6KC1 Mitogen-activated protein kinase (EC 2.7.11.24) Extracellular signal-regulated (MAPK1, MAPK3, MAPK4, MAPK6, MAPK7, MAPK12, MAPK15), C-Jun N-terminal (MAPK8, MAPK9, MAPK10), P38 mitogen-activated protein (MAPK11, MAPK13, MAPK14) MAP3K (EC 2.7.11.25) MAP kinase kinase kinases (MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8) RAFs (ARAF, BRAF, KSR1, KSR2), MLKs (MAP3K12, MAP3K13, MAP3K9, MAP3K10, MAP3K11, MAP3K7, ZAK), CDC7, MAP3K14 Tau-protein kinase (EC 2.7.11.26) TPK1, TTK, GSK-3 (acetyl-CoA carboxylase) kinase (EC 2.7.11.27) - Tropomyosin kinase (EC 2.7.11.28) - Low-density-lipoprotein receptor kinase (EC 2.7.11.29) - Receptor protein serine/threonine kinase (EC 2.7.11.30) Bone morphogenetic protein receptors (BMPR1, BMPR1A, BMPR1B, BMPR2), ACVR1, ACVR1B, ACVR1C, ACVR2A, ACVR2B, ACVRL1, Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)
MAP2K MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7

B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6