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Second messengers derived from inositol lipids
1Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Journal of Bioenergetics and Biomembranes
|February 1, 1991
Summary
Hormones and growth factors trigger cell responses by breaking down plasma-membrane phosphoinositides, generating key second messengers like inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and diacylglycerol. This process involves calcium signaling and impacts cellular growth and proliferation.
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Biochemistry
Background:
- Hormones, growth factors, and neurotransmitters activate target cells via phosphoinositide hydrolysis.
- This process generates second messengers diacylglycerol and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3].
- Ligand-receptor interactions activate phospholipases through G proteins or tyrosine phosphorylation.
Purpose of the Study:
- To elucidate the complexity of the phosphoinositide-calcium signaling system.
- To understand the roles of various enzymes and receptors in this pathway.
- To explore the involvement of phosphoinositides in cellular growth and proliferation.
Main Methods:
- Cloning of phospholipase-C isozymes.
- Cloning of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-5 kinase.
- Cloning of the inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptor.
Main Results:
- The cloning efforts have clarified aspects of the phosphoinositide-calcium signaling system's diversity and complexity.
- Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] induces calcium release from intracellular stores, followed by extracellular calcium influx.
- Phospholipids and their metabolites are increasingly implicated in growth factor and oncogene actions.
Conclusions:
- The phosphoinositide-calcium pathway is crucial for hormonal responses like secretion and contraction.
- This signaling system plays a significant role in regulating cellular growth and proliferation.
- Further research into the cloned components will deepen our understanding of this complex pathway.