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Hormone effects on cellular Ca2+ fluxes.

J R Williamson1, J R Monck

  • 1Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104.

Annual Review of Physiology
|January 1, 1989
PubMed
Summary

Inositol lipid metabolism regulates calcium (Ca2+) signaling via inositol 1,4,5-trisphosphate (Ins 1,4,5-P3). This pathway involves complex feedback mechanisms, including Ca2+ and protein kinase C, to control Ca2+ oscillations.

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Area of Science:

  • Cellular Biology
  • Biochemistry
  • Signal Transduction

Background:

  • Inositol lipid metabolism is crucial for agonist-mediated calcium (Ca2+) signaling.
  • Key proteins in plasma membrane signal transduction, including G proteins, phospholipases, and inositol lipid kinases, have been identified and characterized.
  • An inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) receptor involved in Ca2+ release from intracellular stores has been purified.

Purpose of the Study:

  • To elucidate the mechanisms of agonist-mediated Ca2+ signaling.
  • To understand the role of inositol lipid metabolism and Ins 1,4,5-P3 in Ca2+ signaling.
  • To investigate the feedback regulation of the Ca2+ signaling pathway.

Main Methods:

  • Purification and characterization of signaling proteins.
  • Identification of the Ins 1,4,5-P3 receptor and its role in Ca2+ efflux.
  • Investigation of Ca2+ entry mechanisms and the involvement of second messengers.
  • Analysis of feedback regulation by Ca2+ and protein kinase C.

Main Results:

  • The Ins 1,4,5-P3 receptor mediates Ca2+ efflux from intracellular stores, possibly located in calciosomes.
  • Ca2+ mobilizing agonists stimulate Ca2+ entry, but the activation mechanism of voltage-insensitive Ca2+ channels remains unclear.
  • The Ca2+ signaling pathway exhibits multisite feedback regulation by Ca2+ and diacylglycerol-activated protein kinase C.
  • Ca2+ and protein kinase C provide negative feedback, suggesting complex regulation of Ca2+ oscillations.

Conclusions:

  • Inositol lipid metabolism, particularly Ins 1,4,5-P3 signaling, is central to Ca2+ homeostasis.
  • Complex feedback loops involving Ca2+ and protein kinase C are essential for regulating Ca2+ signaling dynamics, including oscillations.
  • Further research is needed to fully define the role of calciosomes and the precise mechanisms of Ca2+ entry.

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