Phosphorylated Form of Activated IKKbeta and Pancreatic Cancer

项目摘要/摘要 激酶是有吸引力的药物靶点，最近FDA批准的激酶的数量证明了这一点 癌症治疗的抑制剂。目前在诊所的药物要么是针对过度表达的激酶，要么是针对 与疾病有牵连的突变的激酶。然而，并不是所有可用药的激酶都会发生突变或 在许多情况下，它们的活性通过翻译后修饰而改变。其他人和我们 已经发现与正常组织相比，肿瘤样本中的磷酸化IKK水平升高 提示IKK的病态存在磷酸化状态。IKK？和其他激酶一样，受 顺序的磷酸化-去磷酸化事件。缺乏针对该蛋白的磷酸化特异性抗体 各种形式的IKK磷酸化使得定义疾病状态成为一项具有挑战性的努力。在这 应用程序我们将使用一种新技术NanoPro 1000来解决胰腺肿瘤和细胞中的这个问题 台词。这是一个探索性的项目，因为我们试图描述各种翻译后修改的特征 与一种疾病相关的激酶相关。我们的重点是ikk的具体形式，而不是一般的ikk？， 这让这件麻烦事变得新颖和创新。

Project Summary / Abstract Kinases are attractive drug targets as evidenced by the number of recent FDA approvals of kinase inhibitors for cancer therapy. The drugs currently in the clinics are against either overexpressed kinases or mutated kinases that are implicated in the disease. However not all druggable kinases are mutated or overexpressed in many cases their activity altered through post-translational modifications. Others and we have identified elevated levels of phosphorylated IKK¿ in the tumor samples compared to the normal tissues suggesting that the diseased state of IKK¿ exists phosphorylated state. IKK¿ like other kinases is regulated by sequential phosphorylation-dephosphorylation events. The lack of phospho-specific antibodies against the various phosphorylated forms of IKK¿ makes defining the diseased state a challenging endeavor. In this application we will use a novel technology NanoPro 1000 to address this issue in pancreatic tumors and cell lines. This is an exploratory project as we seek to characterize the various post-translational modifications associated with a disease relevant kinase. Our focus on the specific forms of IKK¿, rather than IKK¿ in general, makes this bother novel and innovative.