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Calcium in the action of growth factors
Abstract:
The proliferation of cells in vivo and in culture is regulated by polypeptide growth factors, such as epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). Binding of growth factors to their specific cell-surface receptors initiates a cascade of biochemical events in the cell which ultimately leads to DNA synthesis and cell division. Immediate consequences of receptor activation include tyrosine-specific protein phosphorylations, a sustained increase in cytoplasmic pH and a transient rise in cytoplasmic free Ca2+. The PDGF-induced Ca2+ signal is due to Ca2+ release from intracellular stores, whereas EGF seems to activate a voltage-independent Ca2+ channel in the plasma membrane. Monoclonal antibodies to the EGF receptor that stimulate the tyrosine-specific protein kinase fail to raise [Ca2+]i and are not mitogenic for quiescent cells. These results suggest that activation of the EGF receptor tyrosine kinase is not sufficient for the induction of a Ca2+ signal, and that the rise in [Ca2+]i is indispensable for cell proliferation.
Insights
Cell proliferation relies on growth factors like EGF and PDGF. A rise in intracellular calcium (Ca2+) is essential for this process, indicating it
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cell proliferation is regulated by polypeptide growth factors, including epidermal growth factor (EGF) and platelet-derived growth factor (PDGF).
- Growth factor receptor activation triggers intracellular biochemical events, leading to DNA synthesis and cell division.
- Key early events include protein phosphorylation, increased cytoplasmic pH, and a rise in intracellular calcium (Ca2+).
Purpose of the Study:
- To investigate the role of intracellular calcium (Ca2+) in growth factor-induced cell proliferation.
- To differentiate the mechanisms of Ca2+ signaling induced by EGF and PDGF.
- To determine if EGF receptor tyrosine kinase activation is sufficient for mitogenesis.
Main Methods:
- Utilized monoclonal antibodies targeting the EGF receptor.
- Assessed tyrosine-specific protein kinase activity.
- Measured intracellular calcium ([Ca2+]i) levels and mitogenic responses in quiescent cells.
Main Results:
- PDGF-induced Ca2+ signals originate from intracellular stores.
- EGF signaling appears to involve a plasma membrane calcium channel.
- EGF receptor antibodies activating kinase activity did not elevate [Ca2+]i or induce proliferation.
Conclusions:
- Activation of the EGF receptor tyrosine kinase alone is insufficient for inducing cell proliferation.
- The observed rise in intracellular calcium ([Ca2+]i) is indispensable for growth factor-mediated cell division.
- Distinct Ca2+ signaling pathways are activated by different growth factors.