Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation

Nobuyuki Bokui; Takayuki Otani; Koichi Igarashi; Junichiro Kaku; Mitsuo Oda; Tadahiro Nagaoka; Masaharu Seno; Kenji Tatematsu; Toshihide Okajima; Takashi Matsuzaki; Kang Ting; Katsuyuki Tanizawa; Shun'ichi Kuroda

doi:10.1016/j.febslet.2007.12.006

Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation

Nobuyuki Bokui, Takayuki Otani, Koichi Igarashi, Junichiro Kaku, Mitsuo Oda, Tadahiro Nagaoka, Masaharu Seno, Kenji Tatematsu, Toshihide Okajima, Takashi Matsuzaki, Kang Ting, Katsuyuki Tanizawa, Shun'ichi Kuroda

Research output: Contribution to journal › Article › peer-review

70 Citations (Scopus)

Abstract

NELL1 is an extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells. To elucidate the intracellular signaling cascade evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK signaling cascade, induces the phosphorylation of Runx2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins. Unlike BMP2, NELL1 protein does not activate the Smad signaling cascade. These findings suggest that upon binding to a specific receptor NELL1 transduces an osteogenic signal through activation of certain Tyr-kinases associated with the Ras-MAPK cascade, and finally leads to the osteogenic differentiation.

Original language	English
Pages (from-to)	365-371
Number of pages	7
Journal	FEBS Letters
Volume	582
Issue number	2
DOIs	https://doi.org/10.1016/j.febslet.2007.12.006
Publication status	Published - Jan 23 2008

Keywords

Bone
Differentiation
MAP kinase
Osteoblast
Tyrosine phosphorylation

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2007.12.006

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title = "Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation",

abstract = "NELL1 is an extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells. To elucidate the intracellular signaling cascade evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK signaling cascade, induces the phosphorylation of Runx2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins. Unlike BMP2, NELL1 protein does not activate the Smad signaling cascade. These findings suggest that upon binding to a specific receptor NELL1 transduces an osteogenic signal through activation of certain Tyr-kinases associated with the Ras-MAPK cascade, and finally leads to the osteogenic differentiation.",

keywords = "Bone, Differentiation, MAP kinase, Osteoblast, Tyrosine phosphorylation",

author = "Nobuyuki Bokui and Takayuki Otani and Koichi Igarashi and Junichiro Kaku and Mitsuo Oda and Tadahiro Nagaoka and Masaharu Seno and Kenji Tatematsu and Toshihide Okajima and Takashi Matsuzaki and Kang Ting and Katsuyuki Tanizawa and Shun'ichi Kuroda",

note = "Funding Information: We thank Prof. Ryutaro Kamijo (Showa University Dental School) for helpful discussion and Prof. Takenobu Katagiri (Saitama Medical University) for supplying the Id1 vectors. This study was supported in part by a Grant-in-Aid from JSPS (to SK; No. 15300126). ",

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doi = "10.1016/j.febslet.2007.12.006",

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T1 - Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation

AU - Bokui, Nobuyuki

AU - Otani, Takayuki

AU - Igarashi, Koichi

AU - Kaku, Junichiro

AU - Oda, Mitsuo

AU - Nagaoka, Tadahiro

AU - Seno, Masaharu

AU - Tatematsu, Kenji

AU - Okajima, Toshihide

AU - Matsuzaki, Takashi

AU - Ting, Kang

AU - Tanizawa, Katsuyuki

AU - Kuroda, Shun'ichi

N1 - Funding Information: We thank Prof. Ryutaro Kamijo (Showa University Dental School) for helpful discussion and Prof. Takenobu Katagiri (Saitama Medical University) for supplying the Id1 vectors. This study was supported in part by a Grant-in-Aid from JSPS (to SK; No. 15300126).

PY - 2008/1/23

Y1 - 2008/1/23

N2 - NELL1 is an extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells. To elucidate the intracellular signaling cascade evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK signaling cascade, induces the phosphorylation of Runx2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins. Unlike BMP2, NELL1 protein does not activate the Smad signaling cascade. These findings suggest that upon binding to a specific receptor NELL1 transduces an osteogenic signal through activation of certain Tyr-kinases associated with the Ras-MAPK cascade, and finally leads to the osteogenic differentiation.

AB - NELL1 is an extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells. To elucidate the intracellular signaling cascade evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK signaling cascade, induces the phosphorylation of Runx2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins. Unlike BMP2, NELL1 protein does not activate the Smad signaling cascade. These findings suggest that upon binding to a specific receptor NELL1 transduces an osteogenic signal through activation of certain Tyr-kinases associated with the Ras-MAPK cascade, and finally leads to the osteogenic differentiation.

KW - Bone

KW - Differentiation

KW - MAP kinase

KW - Osteoblast

KW - Tyrosine phosphorylation

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Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation

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Keywords

ASJC Scopus subject areas

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