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 journalArticlepeer-review

70 Citations (Scopus)


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 languageEnglish
Pages (from-to)365-371
Number of pages7
JournalFEBS Letters
Issue number2
Publication statusPublished - 23-01-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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