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A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor.
Biochem Biophys Res Commun. 2008 Dec 19; 377(3):905-9.BB

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic bone formation in muscle tissues. A common mutation among FOP patients has been identified in ALK2, ALK2(R206H), which encodes a constitutively active bone morphogenetic protein (BMP) receptor. Recently, a unique mutation of ALK2, ALK2(G356D), was identified to be a novel mutation in a Japanese FOP patient who had unique clinical features. Over-expression of ALK2(G356D) induced phosphorylation of Smad1/5/8 and activated Id1-luc and alkaline phosphatase activity in myoblasts. However, the over-expression failed to activate phosphorylation of p38, ERK1/2, and CAGA-luc activity. These ALK2(G356D) activities were weaker than those of ALK2(R206H), and they were suppressed by a specific inhibitor of the BMP-regulated Smad pathway. These findings suggest that ALK2(G356D) induces heterotopic bone formation via activation of a BMP-regulated Smad pathway. The quantitative difference between ALK2(G356D) and ALK2(R206H) activities may have caused the phenotypic differences in these patients.

Authors+Show Affiliations

Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

18952055

Citation

Fukuda, Toru, et al. "A Unique Mutation of ALK2, G356D, Found in a Patient With Fibrodysplasia Ossificans Progressiva Is a Moderately Activated BMP Type I Receptor." Biochemical and Biophysical Research Communications, vol. 377, no. 3, 2008, pp. 905-9.
Fukuda T, Kanomata K, Nojima J, et al. A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor. Biochem Biophys Res Commun. 2008;377(3):905-9.
Fukuda, T., Kanomata, K., Nojima, J., Kokabu, S., Akita, M., Ikebuchi, K., Jimi, E., Komori, T., Maruki, Y., Matsuoka, M., Miyazono, K., Nakayama, K., Nanba, A., Tomoda, H., Okazaki, Y., Ohtake, A., Oda, H., Owan, I., Yoda, T., ... Katagiri, T. (2008). A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor. Biochemical and Biophysical Research Communications, 377(3), 905-9. https://doi.org/10.1016/j.bbrc.2008.10.093
Fukuda T, et al. A Unique Mutation of ALK2, G356D, Found in a Patient With Fibrodysplasia Ossificans Progressiva Is a Moderately Activated BMP Type I Receptor. Biochem Biophys Res Commun. 2008 Dec 19;377(3):905-9. PubMed PMID: 18952055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor. AU - Fukuda,Toru, AU - Kanomata,Kazuhiro, AU - Nojima,Junya, AU - Kokabu,Shoichiro, AU - Akita,Masumi, AU - Ikebuchi,Kenji, AU - Jimi,Eijiro, AU - Komori,Tetsuo, AU - Maruki,Yuichi, AU - Matsuoka,Masaru, AU - Miyazono,Kohei, AU - Nakayama,Konosuke, AU - Nanba,Akira, AU - Tomoda,Hiroshi, AU - Okazaki,Yasushi, AU - Ohtake,Akira, AU - Oda,Hiromi, AU - Owan,Ichiro, AU - Yoda,Tetsuya, AU - Haga,Nobuhiko, AU - Furuya,Hirokazu, AU - Katagiri,Takenobu, Y1 - 2008/10/24/ PY - 2008/10/14/received PY - 2008/10/16/accepted PY - 2008/10/28/pubmed PY - 2008/12/17/medline PY - 2008/10/28/entrez SP - 905 EP - 9 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 377 IS - 3 N2 - Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disorder characterized by progressive heterotopic bone formation in muscle tissues. A common mutation among FOP patients has been identified in ALK2, ALK2(R206H), which encodes a constitutively active bone morphogenetic protein (BMP) receptor. Recently, a unique mutation of ALK2, ALK2(G356D), was identified to be a novel mutation in a Japanese FOP patient who had unique clinical features. Over-expression of ALK2(G356D) induced phosphorylation of Smad1/5/8 and activated Id1-luc and alkaline phosphatase activity in myoblasts. However, the over-expression failed to activate phosphorylation of p38, ERK1/2, and CAGA-luc activity. These ALK2(G356D) activities were weaker than those of ALK2(R206H), and they were suppressed by a specific inhibitor of the BMP-regulated Smad pathway. These findings suggest that ALK2(G356D) induces heterotopic bone formation via activation of a BMP-regulated Smad pathway. The quantitative difference between ALK2(G356D) and ALK2(R206H) activities may have caused the phenotypic differences in these patients. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/18952055/A_unique_mutation_of_ALK2_G356D_found_in_a_patient_with_fibrodysplasia_ossificans_progressiva_is_a_moderately_activated_BMP_type_I_receptor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(08)02046-9 DB - PRIME DP - Unbound Medicine ER -