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Melanocortin-3 receptor activates MAP kinase via PI3 kinase

Biaoxin Chai1, Ji-Yao Li, Weizhen Zhang

  • 1Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.

Regulatory Peptides
|December 26, 2006
PubMed

Insights

Activation of the melanocortin-3 receptor (MC3R) by NDP-MSH triggers ERK1/2 phosphorylation and cellular proliferation in HEK cells. This process involves phosphoinositide 3-kinase (PI3K) signaling.

Area of Science:

  • Cellular and Molecular Biology
  • Endocrinology
  • Pharmacology

Background:

  • The melanocortin-3 receptor (MC3R) is a G protein-coupled receptor involved in various physiological processes.
  • Understanding MC3R signaling pathways is crucial for developing targeted therapeutics.

Purpose of the Study:

  • To investigate the signaling pathways downstream of MC3R activation.
  • To determine the role of MC3R in cellular proliferation and apoptosis.

Main Methods:

  • HEK 293 cells stably expressing human MC3R were treated with the MC3R agonist NDP-MSH.
  • ERK1/2 phosphorylation, cellular proliferation, and apoptosis were measured.
  • Pharmacological inhibitors and antagonists were used to elucidate signaling pathways.

Main Results:

  • NDP-MSH induced dose-dependent ERK1/2 phosphorylation (EC50 = 3.3 ± 1.5 x 10⁻⁹ M) and cellular proliferation (EC50 = 2.1 ± 0.6 x 10⁻⁹ M).
  • ERK1/2 phosphorylation was sensitive to pertussis toxin and the PI3K inhibitor wortmannin, but not Rp-cAMPS, BAPTA-AM, or Myr-PKC.
  • Cellular proliferation was inhibited by AGRP (86-132) and the MEK inhibitor PD98059.
  • NDP-MSH did not affect serum deprivation-induced apoptosis.

Conclusions:

  • MC3R activation stimulates ERK1/2 phosphorylation through a pathway involving PI3K.
  • This PI3K-dependent ERK1/2 phosphorylation pathway mediates cellular proliferation in HEK cells expressing MC3R.
  • MC3R activation does not appear to influence apoptosis in this model system.

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