SHP-1 REGULATION OF THE KU SIGNALING PATHWAY

描述：（改编自申请人的摘要） 该应用程序描述了研究机制 蛋白质酪氨酸调节细胞生长的基础 磷酸酶SHP-1。 SHP-1 是一种含有 SH2 结构域的酪氨酸磷酸酶 已在许多系统中显示出负面监管 受体介导的细胞信号传导途径，因此负面影响 调节细胞生长。它在以下领域得到了最广泛的研究 造血/细胞因子受体、FCgRIIB 和 MCH I 类的背景 NK 细胞上表达的受体，其中 SHP-1 被招募到 酪氨酸磷酸化受体并被激活。调查员有 鉴定出与 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端酪氨酸残基在 SHP-1的核定位； 2) 细胞周期依赖性 SHP-1 与其核结合伙伴的相互作用； 3）角色 这些结合伙伴在激活磷酸酶活性中的作用 SHP-1。通过这些研究，研究者建议确定一个 SHP-1 的核功能有助于其发挥负面作用 细胞生长的调节剂。

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.