Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation |
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Authors: | Bokui Nobuyuki Otani Takayuki Igarashi Koichi Kaku Junichiro Oda Mitsuo Nagaoka Tadahiro Seno Masaharu Tatematsu Kenji Okajima Toshihide Matsuzaki Takashi Ting Kang Tanizawa Katsuyuki Kuroda Shun'ichi |
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Institution: | Department of Structural Molecular Biology, The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan. |
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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. |
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