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Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal growth factor receptor-dependent ERK1/2 activation.

Publication ,  Journal Article
Robidoux, J; Kumar, N; Daniel, KW; Moukdar, F; Cyr, M; Medvedev, AV; Collins, S
Published in: J Biol Chem
December 8, 2006

Catecholamine-stimulated lipolysis is primarily a beta-adrenergic and cAMP-dependent event. In previous studies we established that the beta(3)-adrenergic receptor (beta(3)AR) in adipocytes utilizes a unique mechanism to stimulate extracellular signal-regulated kinases 1 and 2 (ERK) by direct recruitment and activation of Src kinase. Therefore, we investigated the role of the ERK pathway in adipocyte metabolism and found that the beta(3)AR agonist CL316,243 regulates lipolysis through both cAMP-dependent protein kinase (PKA) and ERK. Inhibition of PKA activity completely eliminated lipolysis at low (subnanomolar) CL316,243 concentrations and by 75-80% at higher nanomolar concentrations. The remaining 20-25% of PKA-independent lipolysis, as well as ERK activation, was abolished by inhibiting the activity of either Src (PP2 or small interfering RNA), epidermal growth factor receptor (EGFR with AG1478 or small interfering RNA), or mitogen-activated protein kinase kinase 1 or 2 (MKK1/2 with PD098059). PD098059 inhibited lipolysis by 53% in mice as well. Finally, the effect of estradiol, a reported acute activator of ERK and lipolysis, was also totally prevented by PP2, AG1478, and PD098059. These results suggest that ERK activation by beta(3)AR depends upon Src and epidermal growth factor receptor kinase activities and is responsible for the PKA-independent portion of the lipolytic response. Together these results illustrate the distinct and complementary roles for PKA and ERK in catecholamine-stimulated lipolysis.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 8, 2006

Volume

281

Issue

49

Start / End Page

37794 / 37802

Location

United States

Related Subject Headings

  • src-Family Kinases
  • Tyrphostins
  • Sulfonamides
  • Receptors, Adrenergic, beta-3
  • RNA, Small Interfering
  • Quinazolines
  • Mice
  • Lipolysis
  • Isoquinolines
  • Flavonoids
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Robidoux, J., Kumar, N., Daniel, K. W., Moukdar, F., Cyr, M., Medvedev, A. V., & Collins, S. (2006). Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal growth factor receptor-dependent ERK1/2 activation. J Biol Chem, 281(49), 37794–37802. https://doi.org/10.1074/jbc.M605572200
Robidoux, Jacques, Naresh Kumar, Kiefer W. Daniel, Fatiha Moukdar, Michel Cyr, Alexander V. Medvedev, and Sheila Collins. “Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal growth factor receptor-dependent ERK1/2 activation.J Biol Chem 281, no. 49 (December 8, 2006): 37794–802. https://doi.org/10.1074/jbc.M605572200.
Robidoux J, Kumar N, Daniel KW, Moukdar F, Cyr M, Medvedev AV, et al. Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal growth factor receptor-dependent ERK1/2 activation. J Biol Chem. 2006 Dec 8;281(49):37794–802.
Robidoux, Jacques, et al. “Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal growth factor receptor-dependent ERK1/2 activation.J Biol Chem, vol. 281, no. 49, Dec. 2006, pp. 37794–802. Pubmed, doi:10.1074/jbc.M605572200.
Robidoux J, Kumar N, Daniel KW, Moukdar F, Cyr M, Medvedev AV, Collins S. Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal growth factor receptor-dependent ERK1/2 activation. J Biol Chem. 2006 Dec 8;281(49):37794–37802.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 8, 2006

Volume

281

Issue

49

Start / End Page

37794 / 37802

Location

United States

Related Subject Headings

  • src-Family Kinases
  • Tyrphostins
  • Sulfonamides
  • Receptors, Adrenergic, beta-3
  • RNA, Small Interfering
  • Quinazolines
  • Mice
  • Lipolysis
  • Isoquinolines
  • Flavonoids