POSTTRANSLATIONAL MODIFICATION/STRUCTURE-FUNCTION OF BON

描述：（改编自应用程序）。 非胶原性细胞外 基质（ECM）糖基化磷蛋白、骨桥蛋白（OPN）和骨 唾液酸蛋白（BSP），已被假定发挥重要作用，在 骨的形成、吸收和矿化，以及充分的证据 存在表明，这些功能部分是通过 蛋白质的翻译后修饰。 然而，一个明确的 理解含有磷酰基/糖基部分的区域/位点 并且这些区域的功能仍然主要是不确定的。 的 这些蛋白质的功能与蛋白质的相互作用及其对蛋白质的依赖性， 磷酸化状态表明骨的整体质量可能 由于其磷酸化的扰动而作为老化的函数而变化， 从而导致骨骼相关疾病。 很明显， 磷蛋白正变得越来越明显， 成员被发现和调查人员的新利益， 生物科学的一般领域，研究ECM磷蛋白及其 在细胞间通讯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ECM蛋白， 骨测量（OMN）和骨连接蛋白（OCN），具有类似的翻译后 如OPN和BSP的修改。 他们将克隆和表达小说 磷蛋白，OMN和OCN，在细菌和哺乳动物细胞中的后- 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， 该提案的目的是评估和准确界定 磷酸化的浓度、状态和精确位点之间的关系 骨ECM磷蛋白、OPN、BSP、OMN和OCN作为骨龄的函数 和生物矿化程度。因此，我们的目标是定义 生物矿化中的骨丢失和扰动可能 由于衰老和激素缺乏而发生， 糖基化磷蛋白，特别是磷酸化过程， 这样的事件。本文中建议的研究将利用最新技术 和创新的方法开发/率先在这个实验室，以确定 有效和高效地执行具有重要意义的工作 在骨骼生物学中。 这项研究涉及四种蛋白质的研究，其功能是 可能在调节骨骼周转方面具有相当重要的意义 和功能因此，从长远来看，其结果可能导致 开发新的治疗剂、诊断试剂和设备， 主要临床和卫生经济疾病和状况的数量 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.