SHP-1 REGULATION OF THE KU SIGNALING PATHWAY

SHP-1 对 KU 信号通路的调节

• 批准号: 6343071
• 负责人: Taolin Yi
• 金额: $ 15.4万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6343071
• 关键词: biological signal transduction; cell growth regulation; cell nucleus; confocal scanning microscopy; enzyme mechanism; immunofluorescence technique; molecular cloning; natural killer cells; phosphorylation; protein binding; protein localization; protein sequence; protein tyrosine phosphatase; tissue /cell culture; transcription factor

DESCRIPTION: (Adapted from the applicant's abstract) This application describes studies to investigate the mechanism underlying the regulation of cell growth by the protein tyrosine phosphatase SHP-1. SHP-1 is a SH2-domain containing tyrosine phosphatase that has been shown in a number of systems to negatively regulate receptor-mediated cell signaling pathways and therefore negatively regulate cell growth. It has been most extensively studied in the context of hematopoietic/cytokine receptors, FCgRIIB and MCH class I receptors expressed on NK cells, where SHP-1 is recruited to the tyrosine phosphorylated receptor and activated. The investigator has identified nuclear proteins that are associated with SHP-1 and has demonstrated that SHP-1 is found in the nucleus. Dr. Yi proposes to investigate: 1) the role of two C-terminal tyrosine residues in the nuclear localization of SHP-1; 2) the cell cycle dependence on the interaction of SHP-1 with its nuclear binding partners; and 3) the role of these binding partners in activating the phosphatase activity of SHP-1. Through these studies the investigator proposes to identify a nuclear function for SHP-1 that contributes to its role as a negative regulator of cell growth.

描述：（改编自申请人摘要） 本申请描述了研究调查的机制 蛋白酪氨酸调节细胞生长的基础 磷酸酶SHP-1。SHP-1是一种含有SH 2结构域的酪氨酸磷酸酶 在许多系统中， 受体介导的细胞信号传导途径， 调节细胞生长。它已被最广泛的研究， 造血/细胞因子受体、FCgRIIB和MCH I类的背景 NK细胞上表达的SHP-1受体，其中SHP-1被募集到NK细胞上。 酪氨酸磷酸化受体并激活。研究者已 鉴定了与SHP-1相关的核蛋白， 证明SHP-1存在于细胞核中。易博士建议 研究：1）两个C-末端酪氨酸残基在 SHP-1的核定位; 2）细胞周期依赖于SHP-1的核定位。 SHP-1与其核结合伴侣的相互作用;以及3） 这些结合伴侣在激活磷酸酶活性的 SHP-1。通过这些研究，研究人员建议确定一个 SHP-1的核功能，有助于其作为一个负 细胞生长的调节剂。