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Cell-specific cyclic AMP-mediated induction of the PDGF receptor
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, San Diego, CA 92138.
The EMBO Journal
|March 1, 1990
Summary
Elevating cyclic AMP (cAMP) boosts cell proliferation by increasing platelet-derived growth factor (PDGF) receptors. This mechanism explains how cAMP and growth factors synergize to stimulate cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cyclic AMP (cAMP) and polypeptide growth factors synergistically stimulate vertebrate cell proliferation.
- The underlying cellular mechanisms for this cooperative interaction remain largely unknown.
Purpose of the Study:
- To elucidate the cellular mechanisms behind the synergistic proliferation induced by cAMP and growth factors.
- To investigate the role of cAMP in mediating the response to platelet-derived growth factor (PDGF) in Schwann cells.
Main Methods:
- Cultured rat Schwann cells were treated with agents that elevate intracellular cAMP and PDGF.
- Analysis of PDGF receptor mRNA and protein levels.
- Assessment of PDGF receptor autophosphorylation and c-fos gene expression.
Main Results:
- Schwann cell proliferation in response to PDGF was observed only when intracellular cAMP levels were elevated.
- Elevated cAMP dramatically induced PDGF receptor mRNA and protein expression.
- This cAMP-mediated induction enhanced PDGF receptor autophosphorylation and PDGF-stimulated c-fos gene expression.
- The observed induction was specific to cell types where cAMP itself is mitogenic, such as Schwann cells.
Conclusions:
- The synergistic proliferative effect of combining cAMP and polypeptide growth factors is largely due to cAMP-mediated induction of growth factor receptors.
- This mechanism highlights a novel pathway for regulating cell growth and response to external stimuli.