Protein kinase A-mediated cell proliferation in brown preadipocytes is independent of Erk1/2, PI3K and mTOR

Yanling Wang, Masaaki Sato, Yuan Guo, Tore Bengtsson, Jan Nedergaard

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12 Citations (Scopus)


The physiological agonist norepinephrine promotes cell proliferation of brown preadipocytes during the process of tissue recruitment. In a primary culture system, cAMP mediates these adrenergic effects. In the present study, we demonstrated that, in contrast to other systems where the mitogenic effect of cAMP requires the synergistic action of (serum) growth factors, especially insulin/IGF, the cAMP effect in brown preadipocytes was independent of serum and insulin. Protein kinase A, rather than Epac, mediated the cAMP mitogenic effect. The Erk 1/2 family of MAPK, the PI3K system and the mTOR complexes were all activated by cAMP, but these activations were not necessary for cAMP-induced cell proliferation; a protein kinase C isoform may be involved in mediating cAMP-activated cell proliferation. We conclude that the generally acknowledged cellular mediators for induction of cell proliferation are not involved in this process in the brown preadipocyte system; this conclusion may be of relevance both for examination of mechanisms for induction of brown adipose tissue recruitment but also for understanding the mechanism behind e.g. certain endocrine neoplasias.

Original languageEnglish
Pages (from-to)143-155
Number of pages13
JournalExperimental Cell Research
Issue number1
Publication statusPublished - 15 Oct 2014
Externally publishedYes


  • Adrenergic effects
  • Brown adipose tissue
  • CAMP
  • Cell proliferation
  • Erk 1/2
  • MTOR
  • PI3K
  • Protein kinase A

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