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A delayed-early gene activated by fibroblast growth factor-1 encodes a protein related to aldose reductase
P J Donohue1, G F Alberts, B S Hampton
1Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855.
Abstract:
The addition of polypeptide mitogens to quiescent cell lines induces the expression of various gene products, some of which are likely to perform functions critical for cell cycle progression, DNA synthesis, and mitosis. We have used a differential display approach to identify fibroblast growth factor (FGF)-1-inducible genes in NIH-3T3 cells. One of these genes, termed FGF-regulated (FR)-1, encodes a 316-amino acid protein with approximately 82% amino acid sequence identity to an abundant protein expressed in mouse vas deferens and approximately 70% identity to human aldose reductase. The function of the vas deferens protein is unknown; however, aldose reductase is an NADPH-dependent monomeric oxidoreductase implicated in the pathogenesis of diabetic complications. FGF-1 induction of FR-1 mRNA expression is first detectable at 4 h after mitogen addition and is dependent on de novo RNA and protein synthesis. FGF-2 or phorbol ester treatment can also increase FR-1 mRNA levels; in contrast, whole blood serum or individual growth factors present in serum have only minimal effects on FR-1 mRNA expression. FR-1 mRNA is detectable in a number of mouse tissues but is most abundant in newborn liver and in adult intestine, ovary, and testis. These results raise the possibility that aldose reductase-related proteins may play a role in FGF-1- and FGF-2-stimulated mitogenesis.
Insights
Fibroblast growth factor (FGF) induces a novel gene, FR-1, in NIH-3T3 cells. This aldose reductase-related protein may play a role in FGF-stimulated cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Polypeptide mitogens stimulate gene expression in quiescent cells, crucial for cell cycle progression.
- Fibroblast growth factor (FGF) is a key mitogen involved in cellular processes.
- Identifying FGF-inducible genes provides insights into mitogenesis mechanisms.
Purpose of the Study:
- To identify genes induced by fibroblast growth factor-1 (FGF-1) in NIH-3T3 cells.
- To characterize a novel FGF-1-inducible gene, designated FR-1.
- To investigate the potential role of FR-1 in FGF-stimulated cellular responses.
Main Methods:
- Differential display was employed to identify FGF-1-inducible genes.
- FR-1 gene expression was analyzed following FGF-1 stimulation.
- Sequence homology searches were performed to identify related proteins.
- FR-1 mRNA expression was examined in various mouse tissues.
Main Results:
- A novel gene, FR-1, was identified as being induced by FGF-1.
- FR-1 encodes a protein with significant sequence identity to mouse vas deferens protein and human aldose reductase.
- FR-1 mRNA induction by FGF-1 is dependent on de novo RNA and protein synthesis.
- FR-1 mRNA levels are also increased by FGF-2 and phorbol ester, but minimally by serum.
- FR-1 mRNA is found in various mouse tissues, notably abundant in newborn liver and adult intestine, ovary, and testis.
Conclusions:
- The FR-1 gene is rapidly induced by FGF-1 in NIH-3T3 cells.
- The FR-1 protein is related to aldose reductase, an enzyme involved in diabetic complications.
- Aldose reductase-related proteins may participate in FGF-1 and FGF-2-stimulated mitogenesis.