Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation.
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.
Bokui
Nobuyuki
N
Department of Structural Molecular Biology, The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
Otani
Takayuki
T
Igarashi
Koichi
K
Kaku
Junichiro
J
Oda
Mitsuo
M
Nagaoka
Tadahiro
T
Seno
Masaharu
M
Tatematsu
Kenji
K
Okajima
Toshihide
T
Matsuzaki
Takashi
T
Ting
Kang
K
Tanizawa
Katsuyuki
K
Kuroda
Shun'ichi
S
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
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