PROTEIN TYROSINE PHOSPHATASES IN CHRONIC MYELOGENOUS LEUKEMIA

在控制细胞信号传导的背景下， 反应的重点是蛋白激酶和蛋白质的作用， 磷酸化 CML的研究也不例外。 的识别 费城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， 该项目将侧重于对生物多样性的贡献， 蛋白酪氨酸磷酸酶（PTPs）。 该项目提供蛋白质 PTPs研究的化学和分子/细胞生物学方法 与慢性粒细胞白血病的关系 广泛的长期目标 这些研究的目的是识别和表征PTPs作为潜在的 酪氨酸磷酸化异常的拮抗剂， Ph+ CML表型。 该项目的健康相关性是，通过 鉴定和表征了拮抗 p210 bcr/abl的功能，将为p210 bcr/abl的分子生物学研究提供新的视角。 慢性粒细胞白血病的潜在机制和治疗的新的潜在靶点 干预将被发现。 具体目标如下： 1. 确定PTP 1B对p210启动的信号事件的影响 bcr/abl. 2. 从以下方面定义p210 bcr/abl对PTP 1B的影响：a） 表征PTP 1B磷酸化的变化， 在p210 bcr/abl表达后观察到;和B）鉴定和 与PTP 1B相互作用的潜在调节蛋白的表征 以p210 bcr/abl依赖的方式。 3. 检测其他PTP对p210 bcr/abl诱导的信号传导的影响 事件 4. 在CML模型系统和人类患者中表征新型PTP 样品

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.