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Related fibroblast growth factor receptor genes exist in the human genome
E Houssaint1, P R Blanquet, P Champion-Arnaud
1Faculté des Sciences et des Techniques, Université de Nantes, France.
Abstract:
We have isolated, from a human tumor cDNA library, a gene encoding a putative receptor-like protein-tyrosine kinase that we call TK14. The amino acid sequence of the TK14 protein is closely related to the available partial sequence of the mouse protein bek, and more distantly related to the sequences of a chicken basic fibroblast growth factor receptor (73% sequence homology) and the apparent human equivalent of this receptor, the FLG protein (encoded by the fms-like tyrosine kinase gene). Overexpression of the TK14 protein by transfection of COS-1 cells with the corresponding cDNA in a simian virus 40-based expression vector leads to the appearance of new cell-surface binding sites for both acidic and basic fibroblast growth factors. This has been demonstrated by specific binding assays and chemical cross-linking experiments using 125I-labeled growth factors. It appears, therefore, that the human genome contains at least two distinct genes, for TK14 and FLG, that code for related fibroblast growth factor receptors.
Insights
Researchers identified a new gene, TK14, which codes for a protein-tyrosine kinase receptor. This receptor binds fibroblast growth factors, suggesting a role in cell signaling and potentially cancer development.
Area of Science:
- Molecular Biology
- Cell Signaling
- Oncology
Background:
- Fibroblast growth factors (FGFs) are crucial signaling molecules involved in various cellular processes.
- Receptor-like protein-tyrosine kinases play key roles in signal transduction pathways.
- Understanding FGF receptors is vital for deciphering cellular communication and disease mechanisms.
Purpose of the Study:
- To isolate and characterize a novel gene encoding a putative receptor-like protein-tyrosine kinase from a human tumor cDNA library.
- To investigate the functional properties of the identified TK14 protein, particularly its interaction with fibroblast growth factors.
- To determine if TK14 represents a distinct fibroblast growth factor receptor in the human genome.
Main Methods:
- Isolation of the TK14 gene from a human tumor cDNA library.
- Sequence analysis to determine homology with known tyrosine kinases and growth factor receptors.
- Overexpression of TK14 in COS-1 cells using a simian virus 40-based expression vector.
- Specific binding assays and chemical cross-linking experiments using labeled acidic and basic fibroblast growth factors.
Main Results:
- A novel gene, TK14, encoding a putative receptor-like protein-tyrosine kinase was successfully isolated.
- TK14 protein sequence shows close homology to mouse bek and distant homology to chicken and human FGF receptors (FLG).
- Overexpression of TK14 resulted in new cell-surface binding sites for both acidic and basic fibroblast growth factors.
Conclusions:
- The TK14 gene encodes a functional receptor capable of binding fibroblast growth factors.
- The human genome contains at least two distinct genes, TK14 and FLG, coding for related fibroblast growth factor receptors.
- TK14 represents a novel member of the fibroblast growth factor receptor family, with potential implications in cell growth and tumorigenesis.