Different abilities of the four FGFRs to mediate FGF-1 translocation are linked to differences in the receptor C-terminal tail
- PMID: 17003104
- DOI: 10.1242/jcs.03209
Different abilities of the four FGFRs to mediate FGF-1 translocation are linked to differences in the receptor C-terminal tail
Abstract
Members of the fibroblast growth factor family bind to one or more of the four closely related membrane-spanning FGF receptors. In addition to signaling through the receptors, exogenous FGF-1 and FGF-2 are endocytosed and translocated to the cytosol and nucleus where they stimulate RNA and DNA synthesis. Here we have studied the ability of the four FGF receptors to facilitate translocation of exogenous FGF-1 to the cytosol and nucleus. FGFR1 and FGFR4 were able to mediate translocation, whereas FGFR2 and FGFR3 completely lacked this ability. By analyzing mutant FGFRs we found that the tyrosine kinase domain could be deleted from FGFR1 without abolishing translocation, whereas the C-terminal tail of the FGFRs, constituted by approximately 50 amino acids downstream of the kinase domain, plays a crucial role in FGF-1 translocation. Three amino acids residues within the C-terminal tail were found to be of particular importance for translocation. For FGFR2, the two amino acid substitutions Q774M and P800H were sufficient to enable the receptor to support FGF-1 translocation. The results demonstrate a striking diversity in function of the four FGFRs determined by their C-terminal domain.
Similar articles
-
Structural requirements of FGF-1 for receptor binding and translocation into cells.Biochemistry. 2006 Dec 26;45(51):15338-48. doi: 10.1021/bi0618114. Biochemistry. 2006. PMID: 17176056
-
Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4.Oncogene. 2000 Jul 6;19(29):3309-20. doi: 10.1038/sj.onc.1203650. Oncogene. 2000. PMID: 10918587
-
Differential distribution of fibroblast growth factor receptors (FGFRs) on foveal cones: FGFR-4 is an early marker of cone photoreceptors.Mol Vis. 2004 Jan 8;10:1-14. Mol Vis. 2004. PMID: 14737068
-
Cellular signaling by fibroblast growth factor receptors.Cytokine Growth Factor Rev. 2005 Apr;16(2):139-49. doi: 10.1016/j.cytogfr.2005.01.001. Epub 2005 Feb 1. Cytokine Growth Factor Rev. 2005. PMID: 15863030 Review.
-
Structure-function studies of FGF-1: dissociation and partial reconstitution of certain of its biological activities.Mol Reprod Dev. 1994 Sep;39(1):56-60; discussion 60-1. doi: 10.1002/mrd.1080390110. Mol Reprod Dev. 1994. PMID: 7528028 Review.
Cited by
-
Impact of FGF1 on human periodontal ligament fibroblast growth, osteogenic differentiation and inflammatory reaction in vitro.J Orofac Orthop. 2022 Oct;83(Suppl 1):42-55. doi: 10.1007/s00056-021-00363-6. Epub 2021 Dec 7. J Orofac Orthop. 2022. PMID: 34874457 English.
-
FGFR1 clustering with engineered tetravalent antibody improves the efficiency and modifies the mechanism of receptor internalization.Mol Oncol. 2020 Sep;14(9):1998-2021. doi: 10.1002/1878-0261.12740. Epub 2020 Jul 3. Mol Oncol. 2020. PMID: 32511887 Free PMC article.
-
Nucleolin regulates phosphorylation and nuclear export of fibroblast growth factor 1 (FGF1).PLoS One. 2014 Mar 4;9(3):e90687. doi: 10.1371/journal.pone.0090687. eCollection 2014. PLoS One. 2014. PMID: 24595027 Free PMC article.
-
FGFR4 and its novel splice form in myogenic cells: Interplay of glycosylation and tyrosine phosphorylation.J Cell Physiol. 2008 Jun;215(3):803-17. doi: 10.1002/jcp.21365. J Cell Physiol. 2008. PMID: 18186042 Free PMC article.
-
A missense mutation in Fgfr1 causes ear and skull defects in hush puppy mice.Mamm Genome. 2011 Jun;22(5-6):290-305. doi: 10.1007/s00335-011-9324-8. Epub 2011 Apr 10. Mamm Genome. 2011. PMID: 21479780 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous