丝裂原活化蛋白激酶（MAPK）信号分子和Runx2参与NELL1诱导的成骨细胞分化。
Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation.
作者信息
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
机构信息
Department of Structural Molecular Biology, The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
出版信息
FEBS Lett. 2008 Jan 23;582(2):365-71. doi: 10.1016/j.febslet.2007.12.006. Epub 2007 Dec 17.
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.
摘要
NELL1是一种可诱导成骨细胞发生成骨分化和骨形成的细胞外蛋白。为阐明NELL1引发的细胞内信号级联反应，我们已证实NELL1蛋白可短暂激活丝裂原活化蛋白激酶（MAPK）信号级联反应，诱导Runx2磷酸化，并促进酪氨酸磷酸化蛋白在细胞内快速积累。与骨形态发生蛋白2（BMP2）不同，NELL1蛋白不会激活Smad信号级联反应。这些发现表明，NELL1与特定受体结合后，通过激活与Ras-MAPK级联相关的某些酪氨酸激酶来转导成骨信号，最终导致成骨分化。
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