The stimulation of mitogenic signaling pathways by N-POMC peptides

Abstract

The N-terminal fragment of pro-opiomelancortin (POMC) has been shown previously to act as an adrenal mitogen. However, little is known about the molecular mechanisms by which mitogenesis is stimulated, although it has been shown that N-POMC1–28 stimulates the ERK pathway in human H295R cells. We have investigated signaling stimulated by N-POMC1–28 and N-POMC1–49 in the mouse Y1 cell line and found that both peptides stimulate ERK phosphorylation with maximal stimulation being achieved within 5 min. Similar results were observed for both MEK and c-Raf phosphorylation, although N-POMC1–49 stimulated the phosphorylation of Akt more robustly than N-POMC1–28.We also investigated the expression of tyrosine kinase receptors in adrenal cells. PCR utilizing degenerate primers was performed on cDNA from both Y1 cells and rat adrenal tissue. Sequencing of 114 clones from each cDNA population revealed the expression of a number of receptors, several of which have not been described previously in the adrenal.

Progenitor Cell Expansion and Organ Size of Mouse Adrenal Is Regulated by Sonic Hedgehog

“…We examined the anterior pituitary of the conditional KO animals and observed no differences in their development compared with the controls (data not shown). POMC, the precursor of ACTH, which is produced by the anterior pituitary, is known to stimulate proliferation of adrenocortical cells (37,38). We detected no differences in expression of Pomc at P5.…”

60 YEARS OF POMC: Biosynthesis, trafficking, and secretion of pro-opiomelanocortin-derived peptides

“…Metabolic labelling studies and POMC fragment analysis identified that the O-linked glycosylation of Thr-45 regulated the processing of N-POMC(1–77) into N-POMC(1–49) (Bennett 1986), suggesting that stearic hindrance by the sugar moiety could prevent the processing. This has important physiological significance since the regulation of processing that this site produces, controls the level of N-POMC(1–49) and the mitogenic activity it exhibits (Pepper and Bicknell 2009). …”

60 YEARS OF POMC: N-terminal POMC peptides and adrenal growth

“…They also showed that in H295R cells, the peptide decreased steroid hormone production. We carried out a similar study (Pepper & Bicknell 2009) concentrating on Y1 cells and showed stimulation by both synthetic N-POMC(1-28) and purified N-POMC(1-49) resulted in an increase in phosphorylation of both ERKs 1 and 2 as well as their upstream regulators, MEK and c-RAF.…”