scholarly journals Perinuclear localization of an intracellular binding protein related to the fibroblast growth factor (FGF) receptor 1 is temporally associated with the nuclear trafficking of FGF-2 in proliferating epiphyseal growth plate chondrocytes.

Endocrinology ◽  
1996 ◽  
Vol 137 (11) ◽  
pp. 5078-5089 ◽  
Author(s):  
D M Kilkenny ◽  
D J Hill
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Plate ◽  
Binding Protein ◽  
Fibroblast Growth ◽  
Epiphyseal Growth Plate ◽  
Growth Plate Chondrocytes ◽  
Nuclear Trafficking ◽  
Fgf Receptor ◽  
Intracellular Binding

The fibroblast growth factor receptor, FGFR3, forms gradients of intact and degraded protein across the growth plate of developing bovine ribs

2002 ◽  
Vol 361 (2) ◽  
pp. 231-241 ◽  
Author(s):  
Sujata G. PANDIT ◽  
Prasanthi GOVINDRAJ ◽  
Joachim SASSE ◽  
Peter J. NEAME ◽  
John R. HASSELL
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Plate ◽  
Point Mutations ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Hypertrophic Zone ◽  
The Matrix ◽  
Maximum Expression

Point mutations in the human fibroblast growth factor (FGF) receptor 3 gene (Fgfr3) produce a constitutively active receptor, which disrupts chondrocyte differentiation in the growth plate and results in skeletal dysplasias with severe shortening of the limbs. Alternative splicing of the Fgfr3 transcript gives rise to two isoforms, IIIc and IIIb, which vary in their specificity for FGF ligands. We examined the expression of these FGFR3 isoforms in the bovine fetal rib growth plate to determine whether levels of FGFR3 expression are zone-related. Transcripts for both Fgfr3 isoforms are expressed in rib growth plate, with maximum expression in the hypertrophic region and the least expression in the reserve zone. Fgfr3 IIIc is the predominant isoform in the growth plate. Western-blot analysis revealed the presence of full-length FGFR3 (135kDa) for both isoforms in the reserve zone, a major 98kDa fragment in all zones and smaller fragments primarily in the hypertrophic zone. Immunostaining localized FGFR3 to the pericellular region of reserve chondrocytes and to the extracellular matrix in the hypertrophic zone. These results suggest that the transmembrane form of FGFR3 increasingly undergoes proteolytic cleavage towards the hypertrophic zone to produce an extracellular-domain fragment of FGFR3, which is present in large amounts in the matrix of hypertrophic cells. These findings suggest a proteolytic regulatory mechanism for FGFR3, whereby Fgfr3 fragments could control availability of FGF for the intact receptor, and by which proteolysis could inactivate the receptor.

scholarly journals Cloning of an intracellular protein that binds selectively to mitogenic acidic fibroblast growth factor

1998 ◽  
Vol 336 (1) ◽  
pp. 213-222 ◽  
Author(s):  
Elona KOLPAKOVA ◽  
Antoni WIĘDŁOCHA ◽  
Harald STENMARK ◽  
Olav KLINGENBERG ◽  
Pål Ø. FALNES ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
High Efficiency ◽  
Signal Sequence ◽  
Binding Protein ◽  
Fibroblast Growth ◽  
Acidic Fibroblast Growth Factor ◽  
Reading Frame ◽  
Intracellular Binding

In addition to its extracellular action, there is evidence that acidic fibroblast growth factor (aFGF) acts inside cells. To identify intracellular proteins interacting with aFGF, we screened a HeLa cell library in the yeast two-hybrid system using pLex-aFGF as a bait. A clone binding to aFGF, but not to the non-mitogenic mutant aFGF-K132E, was isolated and characterized. The insert contained an open reading frame corresponding to a novel protein of 42 kDa. The protein, termed aFGF intracellular binding protein (FIBP), is mainly hydrophilic and does not contain an N-terminal signal sequence. In vitro-translated FIBP bound specifically to a fusion protein of maltose-binding protein and aFGF. FIBP became post-translationally associated with microsomes added to the cell-free protein synthesizing system, and the membrane-associated protein bound aFGF with high efficiency. Immunoblots and fluorescence microscopy demonstrated that the protein is present in nuclei and, to a lesser extent, associated with mitochondria and other cytoplasmic membranes. The possibility is discussed that FIBP may be involved in the mitogenic action of aFGF. The nucleotide sequences described in this paper have been submitted to GeneBank database under accession numbers AF010187 (human FIBP) and AF010188 (simian FIBP).

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