Phosphorylated Form of Activated IKKbeta and Pancreatic Cancer

描述(由申请人提供)：最近FDA批准的用于癌症治疗的激酶抑制剂的数量证明，激酶是有吸引力的药物靶点。目前临床上的药物要么是针对与疾病有关的过度表达的蛋白激酶，要么是针对突变的蛋白激酶。然而，并不是所有的可用药激酶都是突变或过度表达的，在许多情况下，它们的活性通过翻译后修饰而改变。其他人和我们发现，与正常组织相比，肿瘤组织中的磷酸化IKK水平升高，这表明IKK的病变状态存在磷酸化状态。与其他激酶一样，IKK受一系列的磷酸化-去磷酸化事件的调节。由于缺乏针对各种磷酸化形式的IKK的磷酸特异性抗体，因此定义疾病状态是一项具有挑战性的努力。在这项应用中，我们将使用一项新技术NanoPro 1000来解决胰腺肿瘤和细胞系中的这个问题。这是一个探索性的项目，因为我们试图表征与疾病相关的激酶相关的各种翻译后修饰。我们把重点放在ikk的具体形式上，而不是一般的ikk？，这使得这一令人烦恼的新奇和创新。

DESCRIPTION (provided by applicant): 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.