A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia

1995 ◽  
Vol 10 (3) ◽  
pp. 357-359 ◽  
Author(s):  
Gary A. Bellus ◽  
Iain McIntosh ◽  
E. Anne Smith ◽  
Arthur S. Aylsworth ◽  
Ilkka Kaitila ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Recurrent Mutation ◽  
Tyrosine Kinase Domain ◽  
Fibroblast Growth

scholarly journals Ubiquitination of Fibroblast Growth Factor Receptor 1 Is Required for Its Intracellular Sorting but Not for Its Endocytosis

2008 ◽  
Vol 19 (8) ◽  
pp. 3390-3403 ◽  
Author(s):  
Ellen Margrethe Haugsten ◽  
Jędrzej Małecki ◽  
Sunniva Maria Stordal Bjørklund ◽  
Sjur Olsnes ◽  
Jørgen Wesche
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Fibroblast Growth ◽  
Recycling Endosomes ◽  
Lysine Residues

Endocytosis and targeting of growth factor receptors for lysosomal degradation have been associated with ubiquitination of the intracellular part of the receptors. To elucidate the role of receptor ubiquitination in internalization and sorting of fibroblast growth factor receptor (FGFR), we constructed several mutants of FGFR1 in which lysines, potential ubiquitination sites, were substituted for arginines. Substitution of all lysine residues in the intracellular part of FGFR1 resulted in inactivation of the tyrosine kinase domain of the receptor. However, several multilysine FGFR1 mutants, where up to 26 of 29 lysines in the intracellular part of the receptor were mutated, retained tyrosine kinase activity. The active multilysine mutants were poorly ubiquitinated, but internalized normally, indicating that ubiquitination of the receptor is not required for endocytosis. In contrast, degradation of the multilysine mutants was dramatically reduced as the mutants were inefficiently transported to lysosomes but rather sorted to recycling endosomes. The altered sorting resulted in sustained signaling. The duration of FGFR1 signaling seems to be tightly regulated by receptor ubiquitination and subsequent sorting to the lysosomes for degradation.

Structures of the Tyrosine Kinase Domain of Fibroblast Growth Factor Receptor in Complex with Inhibitors

Science ◽  
1997 ◽  
Vol 276 (5314) ◽  
pp. 955-960 ◽  
Author(s):  
Moosa Mohammadi ◽  
Gerald McMahon ◽  
Li Sun ◽  
Cho Tang ◽  
Peter Hirth ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Fibroblast Growth

Asn540Thr substitution in the fibroblast growth factor receptor 3 tyrosine kinase domain causing hypochondroplasia

1998 ◽  
Vol 11 (S1) ◽  
pp. S62-S65 ◽  
Author(s):  
Piette P. Deutz-Terlouw ◽  
Monique Losekoot ◽  
Cora M. Aalfs ◽  
Raoul C.M. Hennekam ◽  
Egbert Bakker
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Fibroblast Growth
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