PROTEIN TYROSINE PHOSPHATASES IN CHRONIC MYELOGENOUS LEUKEMIA

在细胞信号控制方面的大量研究工作 回应集中在蛋白激酶和蛋白质的作用上 磷酸化。对慢性粒细胞白血病的研究也不例外。身份的鉴定 费城的染色体将注意力集中在p210的作用上 Bcr/abl蛋白酪氨酸激酶。然而，磷酸化是可逆的 在体内的过程，这个项目将集中在 蛋白酪氨酸磷酸酶(PTPs)。这个项目提供蛋白质 PTPs的化学和分子/细胞生物学研究方法 关于他们参与慢性粒细胞白血病的问题。广泛的、长期的目标 这些研究中的一项是确定和表征PTP为潜在的 酪氨酸磷酸化相关的异常酪氨酸磷酸化拮抗剂 PH+CML表型。该项目与健康相关的是通过 拮抗PtPs的鉴定和性质 P210 bcr/abl的功能，将为研究分子提供新的见解。 慢性粒细胞白血病的发病机制及治疗新靶点 干预将会被发现。具体目标如下： 1.确定PTP1B对p210启动的信号事件的影响 BCR/ABL。 2.从以下方面确定p210 bcr/abl对PTP1B的影响： PTP1B磷酸化变化的特征是 观察p210 bcr/abl的表达；b)鉴定和 与PTP1B相互作用的潜在调控蛋白的特性 以p210 bcr/abl依赖的方式。 3.测试其他PTP对p210 BCR/ABL诱导的信号转导的影响 事件。 4.在CML模型系统中和在人类患者中表征新的PTP 样本。

Much research effort in the context of control of cellular signaling responses focuses on protein kinases and the role of protein phosphorylation. The study of CML is no exception. The identification of the Philadelphia chromosome focussed attention on the role of the p210 bcr/abl protein tyrosine kinase. however phosphorylation is a reversible process in vivo and this project will focus on the contribution of the protein tyrosine phosphatases (PTPs). This project offers protein chemical and molecular/cell biological approaches to the study of PTPs with respect to their involvement in CML. The broad, long term objective of these studies is to identify and characterize PTPs as potential antagonists of the aberrant tyrosine phosphorylation associated with the Ph+ CML phenotype. The health relatedness of the project is that through the identification and characterization of PTPs that antagonize the function of p210 bcr/abl, new insights will be provided into the molecular mechanisms underlying CML and new potential targets for therapeutic intervention will be discovered. The specific aims are as follows: 1. To define the effects of PTP1B on signaling events initiated by p210 bcr/abl. 2. To define the effects of p210 bcr/abl on PTP1B in terms of: a) characterization of the changes in phosphorylation of PTP1B that are observed following expression of p210 bcr/abl; and b) identification nd characterization of potential regulatory proteins that interact with PTP1B in a p210 bcr/abl dependent manner. 3. To test the effects of other PTPs on p210 bcr/abl induced signaling events. 4. To characterize novel PTPs in CML model systems and in human patient samples.