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Serum- and polypeptide growth factor-inducible gene expression in mouse fibroblasts
1Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
Abstract:
Complex cellular processes such as proliferation, differentiation, and apoptosis are regulated in part by extracellular signaling molecules: for example, polypeptide growth factors, cytokines, and peptide hormones. Many polypeptide growth factors exert their mitogenic effects by binding to specific cell surface receptor protein tyrosine kinases. This interaction triggers numerous biochemical responses, including changes in phospholipid metabolism, the activation of a protein phosphorylation cascade, and the enhanced expression of specific immediate-early, delayed-early, or late response genes. In this review, I summarize the major findings obtained from studies investigating the effects of serum or individual polypeptide growth factors on gene expression in murine fibroblasts. Several experimental approaches, including differential hybridization screening of cDNA libraries and differential display, have been employed to identify mRNA species that are expressed at elevated levels in serum- or polypeptide growth factor-stimulated cells. These studies have demonstrated that serum- and growth factor-inducible genes encode a diverse family of proteins, including DNA-binding transcription factors, cytoskeletal and extracellular matrix proteins, metabolic enzymes, secreted chemokines, and serine-threonine kinases. Some of these gene products act as effectors of specific cell cycle functions (e.g., enzymes involved in nucleotide and DNA synthesis), others are required to successfully convert a metabolically inactive cell to a metabolically active cell that will eventually increase in size and then divide (e.g., glucose-metabolizing enzymes), and some actually function as positive or negative regulators of cell cycle progression. In conclusion, research conducted during the past 15 years on serum- and growth factor-regulated gene expression in murine fibroblasts has provided significant insight into mitogenic signal transduction and cell growth control.
Insights
Growth factors regulate cell growth by altering gene expression in mouse fibroblasts. These signaling molecules activate pathways controlling cell division, metabolism, and differentiation, offering insights into cell cycle control.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Extracellular signaling molecules like growth factors, cytokines, and peptide hormones regulate complex cellular processes.
- Polypeptide growth factors often mediate mitogenic effects by binding to cell surface receptor protein tyrosine kinases.
- This binding initiates biochemical responses, including altered phospholipid metabolism, protein phosphorylation cascades, and gene expression changes.
Purpose of the Study:
- To review major findings on the effects of serum and polypeptide growth factors on gene expression in murine fibroblasts.
- To identify mRNA species upregulated in response to serum or growth factor stimulation.
- To understand the role of these regulated genes in cell cycle control and mitogenic signal transduction.
Main Methods:
- Differential hybridization screening of cDNA libraries.
- Differential display techniques to identify differentially expressed genes.
- Analysis of gene products involved in cell cycle functions, metabolism, and regulation.
Main Results:
- Serum and growth factors induce a diverse set of genes in murine fibroblasts.
- Induced genes encode proteins such as transcription factors, cytoskeletal components, metabolic enzymes, and kinases.
- Gene products play roles in nucleotide/DNA synthesis, metabolic activation, cell growth, and cell cycle regulation.
Conclusions:
- Research over 15 years has significantly advanced understanding of serum- and growth factor-regulated gene expression.
- These studies provide crucial insights into mitogenic signal transduction pathways.
- The findings illuminate mechanisms controlling cell growth and proliferation in fibroblasts.