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Fibroblast growth factor receptor-4 splice variants cause deletion of a critical tyrosine
W R van Heumen1, C Claxton, J O Pickles
1Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia. W.vanHeumen@vthrc.uq.edu.au
Abstract:
We have identified two novel isoforms of fibroblast growth factor receptor-4 (FGFR4). They result from alternative splicing of intron 17. Two transcripts, both slightly larger than the one coding for the known mouse FGFR4, are generated. The shortest (FGFR4-17a) includes the 31-most 3'-nucleotides of intron 17; the longest (FGFR4-17b) includes all 114 nucleotides of intron 17. Translation of the FGFR4-17a and FGFR4-17b splice variants predicts that both novel putative FGFR4 isoforms have a truncated C-terminal intracellular tail. The first amino acid residue affected by the insertions in both novel isoforms is Tyr-760, a residue that may play a crucial role in intracellular signaling through stimulation of the phosphatidylinositol-biphosphate pathway.
Insights
Two new fibroblast growth factor receptor-4 (FGFR4) isoforms were discovered due to alternative splicing. These variants, FGFR4-17a and FGFR4-17b, possess truncated intracellular tails, potentially impacting cell signaling pathways.
Area of Science:
- Molecular Biology
- Cell Signaling
Background:
- Fibroblast growth factor receptor-4 (FGFR4) is a key regulator of cellular processes.
- Alternative splicing is a mechanism that generates protein diversity from a single gene.
- Understanding FGFR4 isoforms is crucial for deciphering its role in various biological functions.
Purpose of the Study:
- To identify and characterize novel isoforms of fibroblast growth factor receptor-4 (FGFR4).
- To investigate the structural implications of these novel isoforms on the FGFR4 protein.
Main Methods:
- Analysis of alternative splicing events in the FGFR4 gene.
- Transcriptome analysis to identify novel FGFR4 variants.
- Bioinformatic prediction of protein structure and function.
Main Results:
- Identification of two novel FGFR4 isoforms, FGFR4-17a and FGFR4-17b, arising from alternative splicing of intron 17.
- Both novel isoforms are larger than the known mouse FGFR4 transcript.
- Predicted protein products of FGFR4-17a and FGFR4-17b exhibit a truncated C-terminal intracellular tail, affecting Tyr-760.
Conclusions:
- Alternative splicing of intron 17 generates previously unknown FGFR4 isoforms.
- The truncated intracellular tails of these novel isoforms may alter FGFR4-mediated intracellular signaling.
- Further research is needed to elucidate the functional consequences of these FGFR4 variants.