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.
authors: Department of Structural Molecular Biology, The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
authors: Nobuyuki
authors: N
authors: Bokui
authors: Takayuki
authors: T
authors: Otani
authors: Koichi
authors: K
authors: Igarashi
authors: Junichiro
authors: J
authors: Kaku
authors: Mitsuo
authors: M
authors: Oda
authors: Tadahiro
authors: T
authors: Nagaoka
authors: Masaharu
authors: M
authors: Seno
authors: Kenji
authors: K
authors: Tatematsu
authors: Toshihide
authors: T
authors: Okajima
authors: Takashi
authors: T
authors: Matsuzaki
authors: Kang
authors: K
authors: Ting
authors: Katsuyuki
authors: K
authors: Tanizawa
authors: Shun'ichi
authors: S
authors: Kuroda
mesh_terms: D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology*; D010766:Phosphorylation; D034741:RNA, Small Interfering; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; D050659:Core Binding Factor Alpha 1 Subunit; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C493709:RUNX2 protein, human; C493716:Runx2 protein, mouse; D020928:Mitogen-Activated Protein Kinases