Minority Predoctoral Fellowship Program

少数族裔博士前奖学金计划

• 批准号: 7116468
• 负责人: LAKE N PAUL
• 金额: $ 3.25万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116468
• 关键词: HMG coA reductases; X ray crystallography; alcohol oxidoreductases; bacterial toxins; bioimaging /biomedical imaging; enzyme activity; ephrins; oncoproteins; phosphopeptides; predoctoral investigator; protein tyrosine phosphatase; receptor expression; structural biology

DESCRIPTION (provided by applicant): The low molecular weight tyrosine phosphatase, HCPTP-A, has recently been discovered as having oncogenic characteristics. The oncogenic character of this particular phosphatase has been linked to the ephrin receptor tyrosine kinases, B2, B1 and A2, which in turn have been well documented as playing a vital role in the development of vascular networks ("vascular mimicry") in breast, lung, and prostate cancers. The exact mode of interaction between HCPTP-A and the ephrin receptors remain unknown. Two sites of interactions on the ephrin receptors for HCPTP-A have been postulated: the cystosolic juxtamembrane region and SAM domain. In order to investigate whether or not the SAM domain or the juxtamembrane regions are potential substrates for HCPTP-A, phosphopeptides have been created from the putative sites of interaction. The kinetic characterization of the derived peptides for HCPTP-A, the analysis of which residues of the peptides contribute most to its binding kinetics through an alanine scanning method, and the structural analysis of the peptides and HCPTP-A via x-ray crystallography will be implemented to elucidate whether or not there is a preferential mode of interaction between the ephrin receptors and HCPTP-A.

描述（由申请人提供）：低分子量酪氨酸磷酸酶HCPTP-A最近被发现为具有致癌特征。这种特殊磷酸酶的致癌特性已与ephrin受体酪氨酸激酶B2，B1和A2联系在一起，而乳腺网络（“血管模仿”）在乳腺，肺和肺部和prostate Cancers中发挥了至关重要的作用。 HCPTP-A和Ephrin受体之间的确切相互作用模式仍然未知。已经假定了HCPTP-A上的Ephrin受体相互作用的两个位点：囊肿叶膜区域和SAM结构域。为了研究SAM域或近去膜区域是否是HCPTP-A的潜在底物，已经从推定的相互作用位点创建了磷酸肽。用于HCPTP-A的衍生肽的动力学表征，对哪种肽的残基通过丙氨酸扫描方法对其结合动力学的贡献最大，并且对通过X射线术的肽和HCPTP-A的结构分析将在X射线学上实现或未在其中实现互动的互动模式。