Activation of Statl by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism

Wu-Chou S. Su, Motoo Kitagawa, Ninrong Xue, Bing Xie, Silvio Garofalo, Jay Cho, Chuxia Deng, William A. Horton and Xin-Yuan Fu
Additional contact information
Wu-Chou S. Su: Yale University School of Medicine
Motoo Kitagawa: Yale University School of Medicine
Ninrong Xue: Yale University School of Medicine
Bing Xie: Yale University School of Medicine
Silvio Garofalo: Yale University School of Medicine
Jay Cho: Yale University School of Medicine
Chuxia Deng: Yale University School of Medicine
William A. Horton: Yale University School of Medicine
Xin-Yuan Fu: Yale University School of Medicine

Nature, 1997, vol. 386, issue 6622, 288-292

Abstract: Abstract The achondroplasia class of chondrodysplasias comprises the most common genetic forms of dwarfism in humans and includes achondroplasia, hypochondroplasia and thanatophoric dysplasia types I and II (TDI and TDII), which are caused by different mutations in a fibroblast growth-factor receptor FGFR3 (ref. 1). The molecular mechanism and the mediators of these FGFR3-related growth abnormalities are not known. Here we show that mutant TDII FGFR3 has a constitutive tyrosine kinase activity which can specifically activate the transcription factor Statl (for signal transducer and activator of transcription)2,3. Furthermore, expression of TDII FGFR3 induced nuclear translocation of Statl, expression of the cell-cycle inhibitor p21WAF1/CIP1 , and growth arrest of the cell. Thus, TDII FGFR3 may use Statl as a mediator of growth retardation in bone development. Consistent with this, Statl activation and increased p21WAF1/CIP1 expression was found in the cartilage cells from the TDII fetus, but not in those from the normal fetus. Thus, abnormal STAT activation and p21WAF1/CIP1 expression by the TDII mutant receptor may be responsible for this FGFR3-related bone disease.

Date: 1997
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/386288a0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:386:y:1997:i:6622:d:10.1038_386288a0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/386288a0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().