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Functional characterization of a novel FGFR2 mutation, E731K, in craniosynostosis.
J Cell Biochem. 2012 Feb; 113(2):457-64.JC

Abstract

Craniosynostosis is a condition in which some or all of the sutures in the skull of an infant close prematurely. Fibroblast growth factor receptor 2 (FGFR2) mutations are a well-known cause of craniosynostosis. Many syndromes that comprise craniosynostosis, such as Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome, have one of the phenotypes that have been reported in FGFR2 mutant patients. FGFRs have been reported in four types (FGFR1-4), and upon binding with FGF ligands, signal transduction occurs inside of cells. Activated FGFR stimulates an osteogenic master transcription factor, Runx2, through the MAP kinase and PKC pathways. We obtained a genetic analysis of six Korean patients who have craniosynostosis as a phenotype. All of the patients had at least one mutation in the FGFR2 gene; five of those mutations have already been reported elsewhere, while one mutation is novel and was hypothesized to lead to Apert syndrome. In this study, we reported and functionally analyzed a novel mutation of the FGFR2 gene found in a craniosynostosis patient, E731K. The mutation is in the 2nd tyrosine kinase domain in the C-terminal cytoplasmic region of the molecule. The mutation caused an enhanced phosphorylation of the FGFR2(E731K) and ERK-MAP kinase, the stimulation of transcriptional activity of Runx2, and consequently, the enhancement of osteogenic marker gene expression. We conclude that the substitution of E731K in FGFR2 is a novel mutation that resulted in a constitutive activation of the receptor and ultimately resulted in premature suture obliteration.

Authors+Show Affiliations

Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21928350

Citation

Park, Jounghyen, et al. "Functional Characterization of a Novel FGFR2 Mutation, E731K, in Craniosynostosis." Journal of Cellular Biochemistry, vol. 113, no. 2, 2012, pp. 457-64.
Park J, Park OJ, Yoon WJ, et al. Functional characterization of a novel FGFR2 mutation, E731K, in craniosynostosis. J Cell Biochem. 2012;113(2):457-64.
Park, J., Park, O. J., Yoon, W. J., Kim, H. J., Choi, K. Y., Cho, T. J., & Ryoo, H. M. (2012). Functional characterization of a novel FGFR2 mutation, E731K, in craniosynostosis. Journal of Cellular Biochemistry, 113(2), 457-64. https://doi.org/10.1002/jcb.23368
Park J, et al. Functional Characterization of a Novel FGFR2 Mutation, E731K, in Craniosynostosis. J Cell Biochem. 2012;113(2):457-64. PubMed PMID: 21928350.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional characterization of a novel FGFR2 mutation, E731K, in craniosynostosis. AU - Park,Jounghyen, AU - Park,Ok-Jin, AU - Yoon,Won-Joon, AU - Kim,Hyun-Jung, AU - Choi,Kang-Young, AU - Cho,Tae-Joon, AU - Ryoo,Hyun-Mo, PY - 2011/9/20/entrez PY - 2011/9/20/pubmed PY - 2012/5/2/medline SP - 457 EP - 64 JF - Journal of cellular biochemistry JO - J. Cell. Biochem. VL - 113 IS - 2 N2 - Craniosynostosis is a condition in which some or all of the sutures in the skull of an infant close prematurely. Fibroblast growth factor receptor 2 (FGFR2) mutations are a well-known cause of craniosynostosis. Many syndromes that comprise craniosynostosis, such as Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome, have one of the phenotypes that have been reported in FGFR2 mutant patients. FGFRs have been reported in four types (FGFR1-4), and upon binding with FGF ligands, signal transduction occurs inside of cells. Activated FGFR stimulates an osteogenic master transcription factor, Runx2, through the MAP kinase and PKC pathways. We obtained a genetic analysis of six Korean patients who have craniosynostosis as a phenotype. All of the patients had at least one mutation in the FGFR2 gene; five of those mutations have already been reported elsewhere, while one mutation is novel and was hypothesized to lead to Apert syndrome. In this study, we reported and functionally analyzed a novel mutation of the FGFR2 gene found in a craniosynostosis patient, E731K. The mutation is in the 2nd tyrosine kinase domain in the C-terminal cytoplasmic region of the molecule. The mutation caused an enhanced phosphorylation of the FGFR2(E731K) and ERK-MAP kinase, the stimulation of transcriptional activity of Runx2, and consequently, the enhancement of osteogenic marker gene expression. We conclude that the substitution of E731K in FGFR2 is a novel mutation that resulted in a constitutive activation of the receptor and ultimately resulted in premature suture obliteration. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/21928350/Functional_characterization_of_a_novel_FGFR2_mutation_E731K_in_craniosynostosis_ L2 - https://doi.org/10.1002/jcb.23368 DB - PRIME DP - Unbound Medicine ER -