The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]

Publication Date:
2018-08-02
Publisher:
The Company of Biologists
Print ISSN:
0950-1991
Electronic ISSN:
1477-9129
Topics:
Biology
Keywords:
Musculoskeletal system
Published by:
http://www.biologists.com/
_version_ 1836399019802230784
autor Iezaki, T., Fukasawa, K., Horie, T., Park, G., Robinson, S., Nakaya, M., Fujita, H., Onishi, Y., Ozaki, K., Kanayama, T., Hiraiwa, M., Kitaguchi, Y., Kaneda, K., Yoneda, Y., Takarada, T., Guo, X. E., Kurose, H., Hinoi, E.
beschreibung Takashi Iezaki, Kazuya Fukasawa, Tetsuhiro Horie, Gyujin Park, Samuel Robinson, Michio Nakaya, Hiroyuki Fujita, Yuki Onishi, Kakeru Ozaki, Takashi Kanayama, Manami Hiraiwa, Yuka Kitaguchi, Katsuyuki Kaneda, Yukio Yoneda, Takeshi Takarada, X. Edward Guo, Hitoshi Kurose, and Eiichi Hinoi Erk5 belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by Mek5, Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrate that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr 249 , which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser 206 in the linker region known to trigger its proteasomal degradation by Smurf1. Smads transcriptionally activated the expression of Sox9 in mesenchymal cells. Accordingly, removal of one Sox9 allele in mesenchymal cells from Erk5-deficient mice rescued some abnormalities of skeletogenesis. These findings highlight the importance of the Mek5-Erk5-Smurf-Smad-Sox9 axis in mammalian skeletogenesis.
citation_standardnr 6312951
datenlieferant ipn_articles
feed_id 1748
feed_publisher The Company of Biologists
feed_publisher_url http://www.biologists.com/
insertion_date 2018-08-02
journaleissn 1477-9129
journalissn 0950-1991
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The Company of Biologists
quelle Development
relation http://dev.biologists.org/cgi/content/short/145/14/dev164004?rss=1
schlagwort Musculoskeletal system
search_space articles
shingle_author_1 Iezaki, T., Fukasawa, K., Horie, T., Park, G., Robinson, S., Nakaya, M., Fujita, H., Onishi, Y., Ozaki, K., Kanayama, T., Hiraiwa, M., Kitaguchi, Y., Kaneda, K., Yoneda, Y., Takarada, T., Guo, X. E., Kurose, H., Hinoi, E.
shingle_author_2 Iezaki, T., Fukasawa, K., Horie, T., Park, G., Robinson, S., Nakaya, M., Fujita, H., Onishi, Y., Ozaki, K., Kanayama, T., Hiraiwa, M., Kitaguchi, Y., Kaneda, K., Yoneda, Y., Takarada, T., Guo, X. E., Kurose, H., Hinoi, E.
shingle_author_3 Iezaki, T., Fukasawa, K., Horie, T., Park, G., Robinson, S., Nakaya, M., Fujita, H., Onishi, Y., Ozaki, K., Kanayama, T., Hiraiwa, M., Kitaguchi, Y., Kaneda, K., Yoneda, Y., Takarada, T., Guo, X. E., Kurose, H., Hinoi, E.
shingle_author_4 Iezaki, T., Fukasawa, K., Horie, T., Park, G., Robinson, S., Nakaya, M., Fujita, H., Onishi, Y., Ozaki, K., Kanayama, T., Hiraiwa, M., Kitaguchi, Y., Kaneda, K., Yoneda, Y., Takarada, T., Guo, X. E., Kurose, H., Hinoi, E.
shingle_catch_all_1 The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
Musculoskeletal system
Takashi Iezaki, Kazuya Fukasawa, Tetsuhiro Horie, Gyujin Park, Samuel Robinson, Michio Nakaya, Hiroyuki Fujita, Yuki Onishi, Kakeru Ozaki, Takashi Kanayama, Manami Hiraiwa, Yuka Kitaguchi, Katsuyuki Kaneda, Yukio Yoneda, Takeshi Takarada, X. Edward Guo, Hitoshi Kurose, and Eiichi Hinoi Erk5 belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by Mek5, Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrate that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr 249 , which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser 206 in the linker region known to trigger its proteasomal degradation by Smurf1. Smads transcriptionally activated the expression of Sox9 in mesenchymal cells. Accordingly, removal of one Sox9 allele in mesenchymal cells from Erk5-deficient mice rescued some abnormalities of skeletogenesis. These findings highlight the importance of the Mek5-Erk5-Smurf-Smad-Sox9 axis in mammalian skeletogenesis.
Iezaki, T., Fukasawa, K., Horie, T., Park, G., Robinson, S., Nakaya, M., Fujita, H., Onishi, Y., Ozaki, K., Kanayama, T., Hiraiwa, M., Kitaguchi, Y., Kaneda, K., Yoneda, Y., Takarada, T., Guo, X. E., Kurose, H., Hinoi, E.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_2 The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
Musculoskeletal system
Takashi Iezaki, Kazuya Fukasawa, Tetsuhiro Horie, Gyujin Park, Samuel Robinson, Michio Nakaya, Hiroyuki Fujita, Yuki Onishi, Kakeru Ozaki, Takashi Kanayama, Manami Hiraiwa, Yuka Kitaguchi, Katsuyuki Kaneda, Yukio Yoneda, Takeshi Takarada, X. Edward Guo, Hitoshi Kurose, and Eiichi Hinoi Erk5 belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by Mek5, Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrate that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr 249 , which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser 206 in the linker region known to trigger its proteasomal degradation by Smurf1. Smads transcriptionally activated the expression of Sox9 in mesenchymal cells. Accordingly, removal of one Sox9 allele in mesenchymal cells from Erk5-deficient mice rescued some abnormalities of skeletogenesis. These findings highlight the importance of the Mek5-Erk5-Smurf-Smad-Sox9 axis in mammalian skeletogenesis.
Iezaki, T., Fukasawa, K., Horie, T., Park, G., Robinson, S., Nakaya, M., Fujita, H., Onishi, Y., Ozaki, K., Kanayama, T., Hiraiwa, M., Kitaguchi, Y., Kaneda, K., Yoneda, Y., Takarada, T., Guo, X. E., Kurose, H., Hinoi, E.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_3 The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
Musculoskeletal system
Takashi Iezaki, Kazuya Fukasawa, Tetsuhiro Horie, Gyujin Park, Samuel Robinson, Michio Nakaya, Hiroyuki Fujita, Yuki Onishi, Kakeru Ozaki, Takashi Kanayama, Manami Hiraiwa, Yuka Kitaguchi, Katsuyuki Kaneda, Yukio Yoneda, Takeshi Takarada, X. Edward Guo, Hitoshi Kurose, and Eiichi Hinoi Erk5 belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by Mek5, Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrate that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr 249 , which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser 206 in the linker region known to trigger its proteasomal degradation by Smurf1. Smads transcriptionally activated the expression of Sox9 in mesenchymal cells. Accordingly, removal of one Sox9 allele in mesenchymal cells from Erk5-deficient mice rescued some abnormalities of skeletogenesis. These findings highlight the importance of the Mek5-Erk5-Smurf-Smad-Sox9 axis in mammalian skeletogenesis.
Iezaki, T., Fukasawa, K., Horie, T., Park, G., Robinson, S., Nakaya, M., Fujita, H., Onishi, Y., Ozaki, K., Kanayama, T., Hiraiwa, M., Kitaguchi, Y., Kaneda, K., Yoneda, Y., Takarada, T., Guo, X. E., Kurose, H., Hinoi, E.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_4 The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
Musculoskeletal system
Takashi Iezaki, Kazuya Fukasawa, Tetsuhiro Horie, Gyujin Park, Samuel Robinson, Michio Nakaya, Hiroyuki Fujita, Yuki Onishi, Kakeru Ozaki, Takashi Kanayama, Manami Hiraiwa, Yuka Kitaguchi, Katsuyuki Kaneda, Yukio Yoneda, Takeshi Takarada, X. Edward Guo, Hitoshi Kurose, and Eiichi Hinoi Erk5 belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by Mek5, Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrate that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr 249 , which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser 206 in the linker region known to trigger its proteasomal degradation by Smurf1. Smads transcriptionally activated the expression of Sox9 in mesenchymal cells. Accordingly, removal of one Sox9 allele in mesenchymal cells from Erk5-deficient mice rescued some abnormalities of skeletogenesis. These findings highlight the importance of the Mek5-Erk5-Smurf-Smad-Sox9 axis in mammalian skeletogenesis.
Iezaki, T., Fukasawa, K., Horie, T., Park, G., Robinson, S., Nakaya, M., Fujita, H., Onishi, Y., Ozaki, K., Kanayama, T., Hiraiwa, M., Kitaguchi, Y., Kaneda, K., Yoneda, Y., Takarada, T., Guo, X. E., Kurose, H., Hinoi, E.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_title_1 The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
shingle_title_2 The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
shingle_title_3 The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
shingle_title_4 The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
timestamp 2025-06-30T23:36:19.830Z
titel The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
titel_suche The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis [RESEARCH ARTICLE]
topic W
uid ipn_articles_6312951