CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by d'Avis, P. Y.
Right arrow Articles by Donoghue, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by d'Avis, P. Y.
Right arrow Articles by Donoghue, D. J.

Cell Growth & Differentiation, Vol 9, Issue 1 71-78, Copyright © 1998 by American Association of Cancer Research


ARTICLES

Constitutive activation of fibroblast growth factor receptor 3 by mutations responsible for the lethal skeletal dysplasia thanatophoric dysplasia type I

PY d'Avis, SC Robertson, AN Meyer, WM Bardwell, MK Webster and DJ Donoghue
Department of Chemistry and Biochemistry, Center for Molecular Genetics, University of California at San Diego, La Jolla 92093-0367, USA.

Thanatophoric dysplasia type I (TDI) is a neonatal lethal skeletal dysplasia caused by several mutations in the extracellular domain of fibroblast growth factor receptor 3. These mutations occur either in the Ig2-Ig3 linker domain or in the extracellular juxtamembrane domain, and all involve mutation of the wild-type residue to Cys. In all cases, the presence of the mutant Cys residue allows the receptor to dimerize abnormally, resulting in ligand-independent activation. This is also manifested by increased biological signaling, increased tyrosine phosphorylation, and in vitro kinase activity associated with dimeric receptors. These results suggest that TDI is caused by Cys-mediated intermolecular disulfide bonding, leading to constitutive receptor activation as a result of these mutations. Mutations causing TDI are discussed with respect to activating mutations in other receptors that are implicated in human disease.


This article has been cited by other articles:


Home page
Mol Cancer ResHome page
E. di Martino, G. Kelly, J.-A. Roulson, and M. A. Knowles
Alteration of Cell-Cell and Cell-Matrix Adhesion in Urothelial Cells: An Oncogenic Mechanism for Mutant FGFR3
Mol. Cancer Res., January 1, 2015; 13(1): 138 - 148.
[Abstract] [Full Text] [PDF]


Home page
Mol Cancer ResHome page
R. Gyanchandani, M. V. Ortega Alves, J. N. Myers, and S. Kim
A Proangiogenic Signature Is Revealed in FGF-Mediated Bevacizumab-Resistant Head and Neck Squamous Cell Carcinoma
Mol. Cancer Res., December 1, 2013; 11(12): 1585 - 1596.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
R. G. Liao, J. Jung, J. Tchaicha, M. D. Wilkerson, A. Sivachenko, E. M. Beauchamp, Q. Liu, T. J. Pugh, C. S. Pedamallu, D. N. Hayes, et al.
Inhibitor-Sensitive FGFR2 and FGFR3 Mutations in Lung Squamous Cell Carcinoma
Cancer Res., August 15, 2013; 73(16): 5195 - 5205.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
H. Greulich, B. Kaplan, P. Mertins, T.-H. Chen, K. E. Tanaka, C.-H. Yun, X. Zhang, S.-H. Lee, J. Cho, L. Ambrogio, et al.
Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2
PNAS, September 4, 2012; 109(36): 14476 - 14481.
[Abstract] [Full Text] [PDF]


Home page
Biochem. J.Home page
J. Wesche, K. Haglund, and E. M. Haugsten
Fibroblast growth factors and their receptors in cancer
Biochem. J., July 15, 2011; 437(2): 199 - 213.
[Abstract] [Full Text] [PDF]


Home page
DMMHome page
I. Ahmad, L. B. Singh, M. Foth, C.-A. Morris, M. M. Taketo, X.-R. Wu, H. Y. Leung, O. J. Sansom, and T. Iwata
K-Ras and {beta}-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder
Dis. Model. Mech., July 1, 2011; 4(4): 548 - 555.
[Abstract] [Full Text] [PDF]


Home page
Mol Cancer ResHome page
E. M. Haugsten, A. Wiedlocha, S. Olsnes, and J. Wesche
Roles of Fibroblast Growth Factor Receptors in Carcinogenesis
Mol. Cancer Res., November 1, 2010; 8(11): 1439 - 1452.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. E. Ruhe, S. Streit, S. Hart, C.-H. Wong, K. Specht, P. Knyazev, T. Knyazeva, L. S. Tay, H. L. Loo, P. Foo, et al.
Genetic Alterations in the Tyrosine Kinase Transcriptome of Human Cancer Cell Lines
Cancer Res., December 1, 2007; 67(23): 11368 - 11376.
[Abstract] [Full Text] [PDF]


Home page
Cell Growth Differ.Home page
D. J. Penington, I. Bryant, and D. J. Riese II
Constitutively Active ErbB4 and ErbB2 Mutants Exhibit Distinct Biological Activities
Cell Growth Differ., June 1, 2002; 13(6): 247 - 256.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
C. A. Bell, J. A. Tynan, K. C. Hart, A. N. Meyer, S. C. Robertson, and D. J. Donoghue
Rotational Coupling of the Transmembrane and Kinase Domains of the Neu Receptor Tyrosine Kinase
Mol. Biol. Cell, October 1, 2000; 11(10): 3589 - 3599.
[Abstract] [Full Text]


Home page
Cancer Res.Home page
L. Frederick, X.-Y. Wang, G. Eley, and C. D. James
Diversity and Frequency of Epidermal Growth Factor Receptor Mutations in Human Glioblastomas
Cancer Res., March 1, 2000; 60(5): 1383 - 1387.
[Abstract] [Full Text]


Home page
J Biol ChemHome page
J. Labrecque, N. Mc Nicoll, M. Marquis, and A. De Lean
A Disulfide-bridged Mutant of Natriuretic Peptide Receptor-A Displays Constitutive Activity: ROLE OF RECEPTOR DIMERIZATION IN SIGNAL TRANSDUCTION
J. Biol. Chem., April 2, 1999; 274(14): 9752 - 9759.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
N. S. Fracchiolla, S. Luminari, L. Baldini, L. Lombardi, A. T. Maiolo, and A. Neri
FGFR3 Gene Mutations Associated With Human Skeletal Disorders Occur Rarely in Multiple Myeloma
Blood, October 15, 1998; 92(8): 2987 - 2989.
[Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1998 by the American Association of Cancer Research.