alexa The extracellular signal-regulated kinase pathway regulates the phosphorylation of 4E-BP1 at multiple sites.
Diabetes & Endocrinology

Diabetes & Endocrinology

Journal of Obesity & Weight Loss Therapy

Author(s): Herbert TP, Tee AR, Proud CG

Abstract Share this page

Abstract The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), a potent stimulator of Erk, leads to the phosphorylation of 4E-BP1 and its dissociation from eIF4E. In contrast to agonists such as insulin, this occurs independently of PKB activation. In this report, we investigate the mechanism by which TPA regulates 4E-BP1 phosphorylation. Treatment of HEK293 cells with TPA was found to result in the phosphorylation of 4E-BP1 at Ser(64), Thr(69), and Thr(36/45). The TPA-stimulated phosphorylation of all these sites is sensitive to inhibitors of MEK and to the inhibitor of mTOR, rapamycin, indicating that inputs from both mTOR and MEK are required for the regulation of 4E-BP1 phosphorylation by TPA. Indeed, evidence is presented that mTOR may initially be required for the phosphorylation of Thr(45) in a priming step, which is necessary for the subsequent phosphorylation of Ser(64) and Thr(69) through an Erk-dependent pathway. Overexpression of constitutively active MEK in HEK293 cells resulted both in the phosphorylation of 4E-BP1 at Ser(64) and Thr(36/45) and its release from eIF4E. In this case, the phosphorylation of these sites was also blocked by inhibitors of MEK or by rapamycin. In conclusion, the Erk pathway, via mechanisms also requiring mTOR, regulates the phosphorylation of multiple sites in 4E-BP1 in vivo and this is sufficient for the release of 4E-BP1 from eIF4E. This article was published in J Biol Chem and referenced in Journal of Obesity & Weight Loss Therapy

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 13th World Congress on Obesity
    Aug 24-25, 2017, Toronto, Canada
  • 13th Euro Obesity and Endocrinology Congress
    Sep 21-23, 2017, Madrid, Spain
  • 14th Global Obesity Meeting
    Oct 23-24, 2017 Dubai, UAE
  • 16th International Conference and Exhibition on Obesity & Weight Management
    November 13-15, 2017 Atlanta,Georgia, USA

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords