ENGAGEMENT OF THE OSTEOCLAST INTEGRIN ALPHA(V)BETA(3) BY OSTEOPONTIN STIMULATES PHOSPHATIDYLINOSITOL 3-HYDROXYL KINASE-ACTIVITY
ENGAGEMENT OF THE OSTEOCLAST INTEGRIN ALPHA(V)BETA(3) BY OSTEOPONTIN STIMULATES PHOSPHATIDYLINOSITOL 3-HYDROXYL KINASE-ACTIVITY
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DOI：
10.1210/en.136.7.2984
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发表时间：
1995-07-01
期刊：
影响因子：
4.8
通讯作者：
CHERESH, D
中科院分区：
文献类型：
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作者：
HRUSKA, KA;ROLNICK, F;CHERESH, D
破骨细胞通过整合素α（v）β（3）粘附到骨基质蛋白骨桥蛋白（OPN）上，从而刺激骨吸收。我们表征了破骨细胞与 OPN 相互作用时发生的即时信号事件。 OPN 与 alpha(v) beta(3) 结合导致磷酸肌醇 (PtdInsP) 的快速产生，包括三磷酸磷脂酰肌醇 (PtdIns 3,4,5P(3))。 OPN 对 3,4,5-PtdInsP(3) 产生的刺激是通过 PtdInsP 3-OH 激酶活性增加而产生的，该激酶在整合素 α(v) beta(3) 抗体形成的免疫沉淀物中发现。 PtdIns 3-OH 激酶与整联蛋白的关联可能是通过与 c-src 的关联而实现的。后者存在于整合素 α(v) β(3) 抗体形成的免疫沉淀物中，并且 src 激酶被 OPN 激活。这些发现证明了基质蛋白与 α(v) beta(3) 结合后快速产生细胞信号的机制，这类似于酪氨酸激酶生长因子受体使用的机制。
Osteoclast adhesion via integrin alpha(v) beta(3) to the bone matrix protein osteopontin (OPN) results in stimulation of bone resorption. We characterized an immediate signaling event that takes place upon osteoclast interaction with OPN. OPN binding to alpha(v) beta(3) results in the rapid production of the phosphoinositides (PtdInsP), including phosphatidylinositol triphosphate (PtdIns 3,4,5P(3)). Stimulation of 3,4,5-PtdInsP(3) production by OPN was produced by increased activity of PtdInsP 3-OH kinase, which was found in immunoprecipitates formed by antibodies to integrin alpha(v) beta(3). The association of PtdIns 3-OH kinase with integrin may have been through association with c-src. The latter was present in immunoprecipitates formed by the antibodies to integrin alpha(v) beta(3), and src kinase was activated by OPN. These findings demonstrate a mechanism for rapid generation of cell signals upon matrix protein binding to alpha(v) beta(3), which resembles the mechanisms used by tyrosine kinase growth factor receptors.