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Parietal cell MAP kinases: multiple activation pathways

K Nakamura1, C J Zhou, J Parente

  • 1Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta 30912-3175, USA.

The American Journal of Physiology
|October 1, 1996
PubMed
Summary
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Epidermal growth factor (EGF) biphasically activates extracellular signal-regulated kinases (ERKs) 1 and 2 in gastric parietal cells, influencing acid secretion. This pathway is distinct from phosphatidylinositol 3-kinase signaling.

Area of Science:

  • Cellular signaling
  • Gastroenterology
  • Molecular biology

Background:

  • Epidermal growth factor (EGF) exhibits a complex, biphasic effect on gastric parietal cell HCl secretion, involving initial inhibition followed by sustained enhancement.
  • Mitogen-activated protein kinase (MAPK) pathways are implicated in cellular responses to growth factors, but their role in highly differentiated parietal cells is not fully understood.

Purpose of the Study:

  • To investigate the presence and activation mechanisms of MAPK isoforms, specifically extracellular signal-regulated kinases (ERKs) 1 and 2, in gastric parietal cells.
  • To determine the role of ERK activation in mediating the acute and sustained effects of EGF on parietal cell acid secretion.

Main Methods:

  • Primary culture of rabbit gastric parietal cells.
  • Analysis of ERK 1 and 2 activation in response to EGF, phorbol ester (TPA), carbachol, ionomycin, and forskolin.

Related Experiment Videos

  • Investigation of signaling pathways including protein kinase C, phosphatidylinositol 3-kinase, intracellular calcium, and cyclic AMP.
  • Main Results:

    • EGF biphasically activated ERK 1 and 2 in parietal cells, with activation kinetics mirroring EGF's effect on acid secretion.
    • TPA and carbachol also activated ERKs, but through distinct patterns and potentially overlapping pathways.
    • ERK activation was not modulated by intracellular calcium or cAMP levels, and the phosphatidylinositol 3-kinase pathway did not appear to regulate ERK signaling in these cells.

    Conclusions:

    • EGF activates ERKs in gastric parietal cells, contributing to the regulation of acid secretion.
    • Parietal cells utilize distinct signaling pathways for EGF, TPA, and carbachol.
    • The ERK signaling cascade in parietal cells is not directly influenced by phosphatidylinositol 3-kinase, calcium, or cAMP.