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Receptor-operated calcium influx mediated by protein tyrosine kinase pathways
1Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0682, USA.
Abstract:
Calcium influx from the extracellular space elicited by activation of heterotrimeric G protein-coupled and heptahelical receptors plays a critical role in transmembrane signal transduction in a wide variety of cell systems. In nonexcitable cells, the precise voltage-independent mechanism by which calcium enters the cell remains unknown. Multiple mechanisms appear to be operating in different cell types (1-3): 1. G protein-operated calcium influx, 2. Second messenger-operated calcium influx, 3. Capacitative calcium influx, and 4. Phosphorylation of calcium channels. Receptor-operated calcium channels have a fundamental role in stimulus-secretion coupling in many different cells, but these channels remain to be purified and cloned. This review proposes that receptor-operated calcium influx is mediated by protein tyrosine kinase pathways. The function of protein tyrosine kinase pathways and their interactions with other receptor-operated calcium influx mechanisms are described.
Insights
Calcium influx into nonexcitable cells is crucial for cell signaling. This review proposes that protein tyrosine kinase pathways mediate receptor-operated calcium influx, interacting with other known mechanisms.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Biochemistry
Background:
- Calcium influx is vital for transmembrane signal transduction in diverse cell systems.
- The voltage-independent mechanism of calcium entry in nonexcitable cells is not fully understood.
- Existing models include G protein-operated, second messenger-operated, and capacitative calcium influx, alongside channel phosphorylation.
Purpose of the Study:
- To review and propose a unifying mechanism for receptor-operated calcium influx in nonexcitable cells.
- To explore the role of protein tyrosine kinase pathways in mediating calcium entry.
- To describe the interactions between protein tyrosine kinase pathways and other calcium influx mechanisms.
Main Methods:
- Literature review and synthesis of existing research on calcium influx mechanisms.
- Analysis of the proposed role of protein tyrosine kinase pathways in receptor-mediated calcium entry.
- Discussion of the integration of these pathways within the broader context of cellular signaling.
Main Results:
- Receptor-operated calcium channels are essential for stimulus-secretion coupling but remain uncharacterized.
- The review posits that protein tyrosine kinase pathways are a key mediator of receptor-operated calcium influx.
- Interactions between protein tyrosine kinase pathways and other calcium influx mechanisms are highlighted.
Conclusions:
- Protein tyrosine kinase pathways represent a significant mechanism for regulating calcium influx in response to receptor activation.
- Understanding these pathways is critical for elucidating calcium signaling in nonexcitable cells.
- Further research is needed to purify and clone receptor-operated calcium channels.