The structure and function of the FGF receptor isoforms
| Project/Area Number |
03680146
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
ITOH Nobuyuki Kyoto University Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (10110610)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | FGF Receptor / Gene Family / Gene Expression / Growth Factor / aFGF / bFGF / イソフォ-ム |
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| Research Abstract |
Structural analysis of the cDNA for the human fibroblast growth factor receptor (FGFR-1) revealed the existence of a larger and a shorter isoform of the receptor. The larger form has three extracellular immunoglobulin-like domain. Two consecutive amino acids (Arg Met) between the first and second immunoglobulin-like domains are sometimes deleted from the shorter form. We isolated and analyzed the gene for the human fibroblast growth factor receptor. Organization of the gene revealed that the isoforms are produced by two different types of alternative splicing (the cassette and internal donar types) from the common gene. In human placenta, the shorter form is expressed as the major isoform.
We revealed the structure of rat FGF receptor-1 mRNA isoforms and their expression in a variety of rat tissues. The rat FGFR-1 has the characteristics of FGFR-1 as well as mouse, human and chicken homologs. FGFR-1 mRNA was detectable in all the tissues examined by Northern analysis or polymerase chain reaction, indicating that FGFR-1 mRNA is widely expressed in rat tissues.
The rat FGFR-1 mRNA has isoforms in both the extracellular and intracellular regions. The extracellular isoforms which have two or three immunoglobulin-like domains, are expressed almost equally in the tissues except for brain. However, the larger form is a major form in the brain, Furthermore, in the brain, half of FGFR-1 mRNAs have the six nucleotides, which encode s potential serine-threonine kinase phosphorylation site in the intracellular juxtamembrane region, deleted. In contrast to the brain, the deletion isoform is a minor from in the other tissues. The tissue-specific expression of the isoforms indicates that they have different physiological functions. Although other isoforms of FGFR-1 mRNA in tumor cell lines have been reported, the isoforms were undetectable in all rat tissues examined, indicating the isoforms are products of abnormal alternative splicing in tumor cell lines.
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Report
(3 results)
Research Products
(16 results)
