MAPK Signalling in Cellular Metabolism: Stress or Wellness?

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2010 Oct 9

PMID 20930846

Citations 136

Authors

Helmuth Gehart

Susann Kumpf

Arne Ittner

Romeo Ricci

Affiliations

Soon will be listed here.

Abstract

Mitogen-activated protein kinase (MAPK) signalling occurs in response to almost any change in the extracellular or intracellular milieu that affects the metabolism of the cell, organ or the entire organism. MAPK-dependent signal transduction is required for physiological metabolic adaptation, but inappropriate MAPK signalling contributes to the development of several interdependent pathological traits, collectively known as metabolic syndrome. Metabolic syndrome leads to life-threatening clinical consequences, such as type 2 diabetes. This Review provides an overview of the MAPK-signalling mechanisms that underly basic cellular metabolism, discussing their link to disease.

Citing Articles

Choline metabolism disorder induced by Prevotella is a risk factor for endometrial cancer in women with polycystic ovary syndrome.

Chen P, Liu Q, Shi H, Liu Z, Yang X Mol Biol Rep. 2025; 52(1):285.

PMID: 40047940 DOI: 10.1007/s11033-025-10392-8.

Transcriptomics insights into glutamine on repairing of histamine-induced Yak rumen epithelial cells barrier damage in vitro.

Zhang X, Hu R, Wang Z, Wang J, Yue Z, Wu F BMC Genomics. 2025; 26(1):195.

PMID: 40000997 PMC: 11863408. DOI: 10.1186/s12864-025-11383-6.

Regulation and function of insulin and insulin-like growth factor receptor signalling.

Choi E, Duan C, Bai X Nat Rev Mol Cell Biol. 2025; .

PMID: 39930003 DOI: 10.1038/s41580-025-00826-3.

Effects of intrauterine extracellular vesicle microRNAs on embryonic gene expression in low-fertility cows.

Ichikawa R, Kimura K, Nakamura S, Ohkura S, Matsuyama S FASEB J. 2024; 38(20):e70116.

PMID: 39425543 PMC: 11580725. DOI: 10.1096/fj.202401728R.

Unraveling neuronal and metabolic alterations in neurofibromatosis type 1.

Botero V, Tomchik S J Neurodev Disord. 2024; 16(1):49.

PMID: 39217323 PMC: 11365184. DOI: 10.1186/s11689-024-09565-6.

References

Hotamisligil G . Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010; 140(6):900-17. PMC: 2887297. DOI: 10.1016/j.cell.2010.02.034. View

Antonescu C, Huang C, Niu W, Liu Z, Eyers P, Heidenreich K . Reduction of insulin-stimulated glucose uptake in L6 myotubes by the protein kinase inhibitor SB203580 is independent of p38MAPK activity. Endocrinology. 2005; 146(9):3773-81. DOI: 10.1210/en.2005-0404. View

Sabio G, Davis R . cJun NH2-terminal kinase 1 (JNK1): roles in metabolic regulation of insulin resistance. Trends Biochem Sci. 2010; 35(9):490-6. PMC: 2975251. DOI: 10.1016/j.tibs.2010.04.004. View

Taniguchi C, Aleman J, Ueki K, Luo J, Asano T, Kaneto H . The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance. Mol Cell Biol. 2007; 27(8):2830-40. PMC: 1899914. DOI: 10.1128/MCB.00079-07. View

Martin S, Parton R . Lipid droplets: a unified view of a dynamic organelle. Nat Rev Mol Cell Biol. 2006; 7(5):373-8. DOI: 10.1038/nrm1912. View

Bost F, Caron L, Marchetti I, Dani C, Le Marchand-Brustel Y, Binetruy B . Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage. Biochem J. 2002; 361(Pt 3):621-7. PMC: 1222345. DOI: 10.1042/0264-6021:3610621. View

Kaneto H, Nakatani Y, Kawamori D, Miyatsuka T, Matsuoka T, Matsuhisa M . Role of oxidative stress, endoplasmic reticulum stress, and c-Jun N-terminal kinase in pancreatic beta-cell dysfunction and insulin resistance. Int J Biochem Cell Biol. 2005; 37(8):1595-608. DOI: 10.1016/j.biocel.2005.04.003. View

Copps K, Hancer N, Opare-Ado L, Qiu W, Walsh C, White M . Irs1 serine 307 promotes insulin sensitivity in mice. Cell Metab. 2010; 11(1):84-92. PMC: 3314336. DOI: 10.1016/j.cmet.2009.11.003. View

Sumara G, Formentini I, Collins S, Sumara I, Windak R, Bodenmiller B . Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. Cell. 2009; 136(2):235-48. PMC: 2638021. DOI: 10.1016/j.cell.2008.11.018. View

10.

Kim K, Kim J, Wang Y, Sul H . Pref-1 (preadipocyte factor 1) activates the MEK/extracellular signal-regulated kinase pathway to inhibit adipocyte differentiation. Mol Cell Biol. 2007; 27(6):2294-308. PMC: 1820487. DOI: 10.1128/MCB.02207-06. View

11.

Imai J, Katagiri H, Yamada T, Ishigaki Y, Suzuki T, Kudo H . Regulation of pancreatic beta cell mass by neuronal signals from the liver. Science. 2008; 322(5905):1250-4. DOI: 10.1126/science.1163971. View

12.

Font de Mora J, Esteban L, Burks D, Nunez A, Garces C, Garcia-Barrado M . Ras-GRF1 signaling is required for normal beta-cell development and glucose homeostasis. EMBO J. 2003; 22(12):3039-49. PMC: 162132. DOI: 10.1093/emboj/cdg280. View

13.

Ryden M, Arvidsson E, Blomqvist L, Perbeck L, Dicker A, Arner P . Targets for TNF-alpha-induced lipolysis in human adipocytes. Biochem Biophys Res Commun. 2004; 318(1):168-75. DOI: 10.1016/j.bbrc.2004.04.010. View

14.

Juge-Aubry C, Hammar E, PERNIN A, Takeshita A, Chin W, Burger A . Regulation of the transcriptional activity of the peroxisome proliferator-activated receptor alpha by phosphorylation of a ligand-independent trans-activating domain. J Biol Chem. 1999; 274(15):10505-10. DOI: 10.1074/jbc.274.15.10505. View

15.

Deak M, Clifton A, Lucocq L, Alessi D . Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 1998; 17(15):4426-41. PMC: 1170775. DOI: 10.1093/emboj/17.15.4426. View

16.

Hata K, Nishimura R, Ikeda F, Yamashita K, Matsubara T, Nokubi T . Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor gamma during bone morphogenetic protein 2-induced adipogenesis. Mol Biol Cell. 2003; 14(2):545-55. PMC: 149991. DOI: 10.1091/mbc.e02-06-0356. View

17.

Moxham C, Tabrizchi A, Davis R, Malbon C . Jun N-terminal kinase mediates activation of skeletal muscle glycogen synthase by insulin in vivo. J Biol Chem. 1996; 271(48):30765-73. DOI: 10.1074/jbc.271.48.30765. View

18.

Mayr B, Montminy M . Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol. 2001; 2(8):599-609. DOI: 10.1038/35085068. View

19.

Qiao L, MacDougald O, Shao J . CCAAT/enhancer-binding protein alpha mediates induction of hepatic phosphoenolpyruvate carboxykinase by p38 mitogen-activated protein kinase. J Biol Chem. 2006; 281(34):24390-7. DOI: 10.1074/jbc.M603038200. View

20.

Gross D, Wan M, Birnbaum M . The role of FOXO in the regulation of metabolism. Curr Diab Rep. 2009; 9(3):208-14. DOI: 10.1007/s11892-009-0034-5. View