Document Detail


Cell transformation by fibroblast growth factors can be suppressed by truncated fibroblast growth factor receptors.
MedLine Citation:
PMID:  7935480     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ligand-induced dimerization and transphosphorylation are thought to be important events by which receptor tyrosine kinases generate cellular signals. We have investigated the ability of signalling-defective, truncated fibroblast growth factor (FGF) receptors (FGFR-1 and FGFR-2) to block the FGF response in cells that express both types of endogenous FGF receptors. When these dominant negative receptors are expressed in NIH 3T3 cells transformed by the secreted FGF-4, the transformed properties of the cells can be reverted to various degrees, with better reversion phenotype correlating with higher levels of truncated receptor expression. Furthermore, truncated FGFR-2 is significantly more efficient at producing reversion than FGFR-1, indicating that FGF-4 preferentially utilizes the FGFR-2 signalling pathway. NIH 3T3 clones expressing these truncated receptors are more resistant to FGF-induced mitogenesis and also exhibit reduced tyrosine phosphorylation upon treatment with FGF. The block in FGF-signalling, however, can be overcome by the addition of excess growth factor. The truncated receptors have binding affinities that are four- to eightfold lower than those of wild-type receptors, as measured by Scatchard analysis. We also observed a partial specificity in the responses of truncated-receptor-expressing clones to FGF-2 or FGF-4. Our results suggest that the block to signal transduction produced by kinase-negative FGF receptors is achieved through a combination of dominant negative effects and competition for growth factor binding with functional receptors.
Authors:
Y Li; C Basilico; A Mansukhani
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  14     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1994 Nov 
Date Detail:
Created Date:  1994-11-18     Completed Date:  1994-11-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7660-9     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Kaplan Cancer Center, New York University School of Medicine, New York 10016.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Binding Sites
CHO Cells
Cell Transformation, Neoplastic / genetics,  metabolism*
Cricetinae
Fibroblast Growth Factors / genetics,  physiology*
Mice
Mutagenesis
Phenotype
Phosphorylation
Receptors, Fibroblast Growth Factor / genetics,  physiology*
Signal Transduction
Transfection
Grant Support
ID/Acronym/Agency:
CA42568/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Fibroblast Growth Factor; 62031-54-3/Fibroblast Growth Factors
Comments/Corrections

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