Skip to main content
SpringerLink
Log in

Involvement of c-Jun N-terminal kinase activities in skeletal muscle differentiation

  • Published:
Journal of Muscle Research & Cell Motility Aims and scope Submit manuscript

Abstract

Previous studies on skeletal muscle differentiation showed that myogenesis is regulated by extracellular signal-regulated kinases (ERK-1/-2) and p38 mitogen activated kinase (MAPK) pathways. Present study shows that c-Jun NH(2)-terminal protein kinase (JNK) activities were up regulated during skeletal muscle differentiation in rat skeletal muscle L6E9 cells, as determined by Western immunoblot of differentiating cells probed with anti-phospho-JNK antibody. Inhibition of JNK activities by JNK inhibitor II drastically inhibited differentiation as determined by decreased myosin, myogenin expression and creatine kinase activity. The inhibition of the differentiation was regulated by apoptosis as determined by the detection of poly(ADP-ribose) polymerase (PARP) cleavage, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells when JNK activities were inhibited. Apoptosis was accompanied by marked expression and activation of c-Jun and p53 transcription factors. Taken together, our results indicate that basal JNK activities are essential for regulating skeletal muscle differentiation, and inhibition of JNK activation affects myogenesis by apoptosis dependent on c-Jun and p53 transcription factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adams V, Gielen S, Hambrecht R and Schuler G ( 2001) Apoptosis in skeletal muscle. Front Biosci 6: D1–D11.

    Google Scholar 

  • E Bengal L Ransone Scharfmann VJ Dwarki SJ Tapscott H Weintraub IM Verma (1992) ArticleTitleFunctional antagonism between c-Jun and MyoD proteins: a direct physical association Cell 68 507–519 Occurrence Handle10.1016/0092-8674(92)90187-H Occurrence Handle1310896

    Article  PubMed  Google Scholar 

  • BL Bennett DT Sasaki BW Murray EC O’Leary ST Sakata W Xu JC Leisten A Motiwala S Pierce Y Satoh SS Bhagwat AM Manning DW Anderson (2001) ArticleTitleSP600125, an anthra-xpyrazolone inhibitor of Jun N-terminal kinase Proc Natl Acad Sci USA 98 13681–13686 Occurrence Handle10.1073/pnas.251194298 Occurrence Handle11717429

    Article  PubMed  Google Scholar 

  • A Bonni A Brunet AE West SR Datta MA Takasu ME Greenberg (1999) ArticleTitleCell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and independent mechanisms J Biol Chem 286 1358–1362

    Google Scholar 

  • MS Caetano A Vieira-De-Abreu LK Teixeira MB Werneck MA Barcinski JP Viola (2002) ArticleTitleNFATC2 transcription factor regulates cell cycle progression during lymphocyte activation: evidence of its involvement in the control of cyclin gene expression FASEB J 14 1940–1942

    Google Scholar 

  • M Cavigeli F Dolfi FX Claret M Karin (1995) ArticleTitleInduction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation EMBO J 14 5957–5764 Occurrence Handle8846788

    PubMed  Google Scholar 

  • R Craig A Larkin AM Mingo DJ Thuerauf C Andrews PM McDonough CC Glembotski (2000) ArticleTitlep38 MAPK and NF-kappa B collaborate to induce interleukin-6 gene expression and release Evidence for a cytoprotective autocrine signaling pathway in a cardiac myocyte model system. J Biol Chem 275 23814–23824

    Google Scholar 

  • A Cuenda P Cohen (1999) ArticleTitleStress-activated protein kinase-2/p38 and a rapamycin-sensitive pathway are required for C2C12 myogenesis J Biol Chem 274 4341–4346 Occurrence Handle10.1074/jbc.274.7.4341 Occurrence Handle9933636

    Article  PubMed  Google Scholar 

  • RJ Davis (2000) ArticleTitleSignal transduction by the JNK group of MAP kinases Cell 103 239–252 Occurrence Handle10.1016/S0092-8674(00)00116-1 Occurrence Handle11057897

    Article  PubMed  Google Scholar 

  • L Du CS Lyle TB Obey WA Gaarde JA Muir BL Bennett TC Chambers (2004) ArticleTitleInhibition of cell proliferation and cell cycle progression by specific inhibition of basal JNK activity: evidence that mitotic Bcl-2 phosphorylation is JNK-independent J Biol Chem. 279 11957–11966 Occurrence Handle10.1074/jbc.M304935200 Occurrence Handle14704147

    Article  PubMed  Google Scholar 

  • R Eferl M Sibilia F Hilberg A Fuchsbichler I Kufferath B Guertl R Zenz EF Wagner K Zatloukal (1999) ArticleTitleFunctions of c-Jun in liver and heart development J Cell Biol 145 1049–1061 Occurrence Handle10.1083/jcb.145.5.1049 Occurrence Handle10352021

    Article  PubMed  Google Scholar 

  • JR Florini KA Magri DZ Ewton PL James K Grindstaff PS Rotwein (1991) ArticleTitle“Spontaneous” differentiation of skeletal myoblasts is dependent upon autocrine secretion of insulin-like growth factor-II J Biol Chem 266 15917–15923 Occurrence Handle1651927

    PubMed  Google Scholar 

  • SY Fuchs V Adler T Buschmann Z Yin X Wu SN Jones Z Ronai (1998b) ArticleTitleJNK targets p53 ubiquitination and degradation in nonstressed cells Genes Dev 12 2658–2663

    Google Scholar 

  • SY Fuchs V Adler MR Pincus Z Ronai (1998a) ArticleTitleMEKK/JNK signaling stabilizes and activates p53 Proc Natl Acad Sci USA. 95 2586–2591 Occurrence Handle10.1073/pnas.95.5.2586

    Article  Google Scholar 

  • E Gredinger AN Gerber Y Tamir SJ Tapscott E Bengal (1998) ArticleTitleMitogen activated protein kinase pathway is involved in the differentiation of muscle cells J Biol Chem 273 10436–10444 Occurrence Handle10.1074/jbc.273.17.10436 Occurrence Handle9553102

    Article  PubMed  Google Scholar 

  • H Huynh (2002) ArticleTitleInduction of apoptosis in rat ventral prostate by finasteride is associated with alteration in MAP kinase pathways and Bcl-2 related family of proteins Int J Oncol 20 1297–1303 Occurrence Handle12012013

    PubMed  Google Scholar 

  • H Ichijo (1999) ArticleTitleFrom receptors to stress-activated MAP kinases Oncogene 18 6087–6093 Occurrence Handle10.1038/sj.onc.1203129 Occurrence Handle10557099

    Article  PubMed  Google Scholar 

  • A Khurana CS Dey (2002) ArticleTitleSubtype specific roles of mitogen activated protein kinases in L6E9 skeletal muscle cell differentiation Mol Cell Biochem 238 27–39 Occurrence Handle10.1023/A:1019957602038 Occurrence Handle12349907

    Article  PubMed  Google Scholar 

  • ZG Liu R Baskaran ET Lea-Chou LD Wood Y Chen M Karin JYJ Wang (1996a) ArticleTitleThree distinct signalling responses by murine fibroblasts to genotoxic stress Nature 384 273–276 Occurrence Handle10.1038/384273a0

    Article  Google Scholar 

  • ZG Liu H Hsu DV Goddel M Karin (1996b) ArticleTitleDissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappaB activation prevents cell death Cell 87 565–576 Occurrence Handle10.1016/S0092-8674(00)81375-6

    Article  Google Scholar 

  • Gee MM Mc G Campiani A Ramunno V Nacci M Lawler DC Williams DM Zisterer (2002) ArticleTitleActivation of the c-Jun N-terminal kinase (JNK) signaling pathway is essential during PBOX-6-induced apoptosis in chronic myelogenous leukemia (CML) cells J Biol Chem 277 18383–18389 Occurrence Handle10.1074/jbc.M112058200 Occurrence Handle11856743

    Article  PubMed  Google Scholar 

  • T Mosman (1983) ArticleTitleRapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays J Immunol Methods 65 55–63 Occurrence Handle6606682

    PubMed  Google Scholar 

  • G Natoli A Costanzo A Ianni DJ Templeton JR Woodgett C Balsano M Levrero (1997) ArticleTitleActivation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway Science 275 200–203 Occurrence Handle10.1126/science.275.5297.200 Occurrence Handle8985011

    Article  PubMed  Google Scholar 

  • O Potapova M Gorospe RH Dougherty NM Dean WA Gaarde NJ Holbrook (2000) ArticleTitleInhibition of c-Jun N-terminal kinase 2 expression suppresses growth and induces apoptosis of human tumor cells in a p53-dependent manner Mol Cell Biol 20 1713–1722 Occurrence Handle10.1128/MCB.20.5.1713-1722.2000 Occurrence Handle10669748

    Article  PubMed  Google Scholar 

  • C Reinhard B Shamoon V Shyamala LT Williams (1997) ArticleTitleTumor necrosis factor alpha-induced activation of c-Jun N-terminal kinase is mediated by TRAF2 EMBO J 16 1080–1092 Occurrence Handle10.1093/emboj/16.5.1080 Occurrence Handle9118946

    Article  PubMed  Google Scholar 

  • A Roulston C Reinhard P Amiri LT Williams (1998) ArticleTitleEarly activation of c-Jun N-terminal kinase and p38 kinase regulate cell survival in response to tumor necrosis factor alpha J Biol Chem 273 10232–10239 Occurrence Handle10.1074/jbc.273.17.10232 Occurrence Handle9553074

    Article  PubMed  Google Scholar 

  • KM Ryan AC Phillips KH Vousden (2001) ArticleTitleRegulation and function of the p53 tumor suppressor protein Curr Opin Cell Biol 13 332–337 Occurrence Handle10.1016/S0955-0674(00)00216-7 Occurrence Handle11343904

    Article  PubMed  Google Scholar 

  • K Sabapathy W Jochum K Hochedlinger L Chang M Karin EF Wagner (1999) ArticleTitleDefective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2 Mech. Dev 89 115–124 Occurrence Handle10.1016/S0925-4773(99)00213-0 Occurrence Handle10559486

    Article  PubMed  Google Scholar 

  • PK Smith RI Krohn GT Hermanson AK Mallia FH Gartner MD Provenzano EK Fujimoto NM Goeke BJ Olson DC Klenk (1985) ArticleTitleMeasurement of protein using bicinchoninic acid Anal Biochem 150 76–85 Occurrence Handle10.1016/0003-2697(85)90442-7 Occurrence Handle3843705

    Article  PubMed  Google Scholar 

  • DD Yang CY Kuan AJ Whitmarsh M Rincon TS Zheng RJ Davis P Rakic RA Flavell (1997) ArticleTitleAbsence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene Nature 389 865–870 Occurrence Handle10.1038/39899 Occurrence Handle9349820

    Article  PubMed  Google Scholar 

  • P Zacchi M Gostissa T Uchida C Salvagno F Avolio S Volinia Z Ronai G Blandino C Schneider GD Sal (2002) ArticleTitleThe prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults Nature 419 853–857 Occurrence Handle10.1038/nature01120 Occurrence Handle12397362

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S NAGAR, 160062, Punjab, India

    Ashwani Khurana & Chinmoy S. Dey

  2. Mount Sinai School of Medicine, Department of Oncological Sciences, Icahn Medical Institute, One Gustav Levy Place, Box 1130, New York, NY, 10029, USA

    Ashwani Khurana

Authors
  1. Ashwani Khurana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chinmoy S. Dey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chinmoy S. Dey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khurana, A., Dey, C.S. Involvement of c-Jun N-terminal kinase activities in skeletal muscle differentiation. J Muscle Res Cell Motil 25, 645–655 (2004). https://doi.org/10.1007/s10974-004-7099-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10974-004-7099-1

Keywords

Search

Navigation