SHP-1 REGULATION OF THE KU SIGNALING PATHWAY

描述：(改编自申请人的摘要) 这项申请描述了研究机制的研究。 酪氨酸蛋白对细胞生长的调节作用 磷酸酶SHP-1。SHP-1是一个含有酪氨酸磷酸酶的SH2结构域 这已经在许多系统中显示出来，以进行负面调控 受体介导的细胞信号通路，因此对 调节细胞生长。对它进行了最广泛的研究 造血/细胞因子受体、FCgRIIB和MCH I类受体的研究背景 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激活。调查员已经 鉴定出与SHP-1相关的核蛋白，并已 证明SHP-1存在于细胞核内。易博士建议 研究：1)两个C-末端酪氨酸残基在细胞周期中的作用 SHP-1的核定位；2)细胞周期依赖于 SHP-1与其核结合伙伴的相互作用；以及3)作用 这些结合伙伴在激活磷酸酶活性方面的作用 SHP-1。通过这些研究，调查员建议确定一种 SHP-1的核功能对其负性作用的贡献 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.