POSTTRANSLATIONAL MODIFICATION/STRUCTURE-FUNCTION OF BON

描述：(改编自应用程序)。非胶原胞外膜 基质(ECM)糖基化磷蛋白、骨桥蛋白(OPN)与骨 唾液酸蛋白(BSP)，已被认为在 骨的形成、吸收和矿化，以及充分的证据 表明这些功能在一定程度上通过 蛋白质的翻译后修饰。然而，一个明确的 了解含有磷基/糖基的区域/部位 这些地区的功能仍然主要是不确定的。这个 这些蛋白质的功能与细胞的偶联及其对细胞的依赖 磷酸化状态表明骨骼的整体质量可能 由于其磷酸化的扰动而作为老化的函数而变化， 从而导致与骨骼相关的疾病。显然，骨细胞外基质的重要性 磷蛋白正变得越来越明显 被发现的成员和调查人员在 细胞外基质磷蛋白及其相关生物科学研究的一般领域 在细胞-细胞交流和细胞-基质相互作用中的作用。这些 研究人员最近发现了两种新的骨骼细胞外基质蛋白， 骨测量(OMN)和骨结素(OCN)，具有相似的翻译后 如OPN和BSP的修改。他们将克隆并表达这部小说 细菌和哺乳动物细胞中的磷蛋白OMN和OCN，用于后 翻译修饰研究，以及OMN和OCN对 破骨细胞形成和成骨细胞矿化。因此，总体上来说， 本提案的目标是准确评估和定义 磷酸化浓度、状态与精确位点的关系 骨ECM磷蛋白、OPN、BSP、OMN和OCN与骨龄的关系 以及生物矿化过程的程度。因此，我们将致力于定义 生物矿化中骨丢失和扰动的机制(S) 由于衰老和荷尔蒙不足而发生的作用 糖基化磷酸蛋白，特别是磷酸化过程，在 这类事件。建议中的研究将利用最新的技术 以及本实验室开发/开创的创新方法，以确定 有效和高效地执行具有重要影响的工作 在骨骼生物学方面。 这项研究涉及四种蛋白质的研究，它们的功能是 可能在骨骼周转的调节中具有相当重要的作用 和功能。因此，从长远来看，结果可能会导致 用于治疗的新疗法、诊断试剂和设备的发展 主要临床和卫生经济的疾病数量和病情 阻塞性骨质疏松症、骨转移、骨折愈合等。

DESCRIPTION: (Adapted from the Application). Non-collagenous extracellular matrix (ECM) glycosylated phosphoproteins, osteopontin (OPN) and bone sialoprotein (BSP), have been postulated to play significant roles in the formation, resorption and mineralization of bone, and sufficient evidence exists to suggest that these functions are in part regulated via post-translational modification of the proteins. However, a clear understanding of the regions/sites that contain phosphoryl/glycosyl moieties and the functions of these regions remain predominantly undefined. The coupling of the functions of these proteins with and their dependence on the state of phosphorylation indicates that the overall quality of the bone may vary as a function of aging due to perturbations in their phosphorylation, thus leading to bone-related disorders. Clearly the importance of bone ECM phosphoproteins is becoming increasingly apparent by the continuing additional members being discovered and the emerging interests of investigators in general fields of biological sciences studying ECM phosphoproteins and their role in cell-cell communication and cell-matrix interactions. These investigators have recently discovered two novel bone ECM proteins, osteometric (OMN) and osteocontin (OCN), with similar post-translational modifications as those of OPN and BSP. They will clone and express the novel phosphoproteins, OMN and OCN, in bacterial and in mammalian cells for post- translational modification studies, and studies on effects of OMN and OCN on osteoclast formation and osteoblast mineralization. Thus, one of the overall objectives of this proposal is to evaluate and define precisely the relationship between concentration, state and precise sites of phosphorylation of bone ECM phosphoproteins, OPN, BSP, OMN and OCN as a function of bone age and extent of biomineralization process. Hence, we will aim to define the mechanism(s) by which bone loss and perturbations in biomineralization may occur as a result of aging and hormonal deficiency and the role of glycosylated phosphoproteins, in particular the process of phosphorylation, in such events. The proposed studies herein will utilize the latest technologies and innovative approaches developed/pioneered in this laboratory to ascertain the effective and efficient execution of the work with important implications in bone biology. This research concerns the study of four proteins, the functions of which are likely to be of considerable importance in the regulation of skeletal turnover and function. As such, the results could, in the long term, lead to the development of new therapeutics, diagnostic reagents and devices for use in a number of diseases and conditions of major clinical and health economical impactosteoporosis, bone metastasis, fracture healing, etc.