Structure/Function of Frizzled-related protein

卷曲相关蛋白的结构/功能

• 批准号: 6559125
• 负责人: JEFFREY RUBIN
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6559125
• 关键词: T lymphocyte; biological signal transduction; cell growth regulation; cell proliferation; developmental genetics; embryo /fetus cell /tissue; embryo /fetus protein; embryogenesis; fibroblast growth factor; gene expression; hepatocyte growth factor; protein structure function; thymus; tissue /cell culture; vertebrate embryology

During the past year, we have continued to focus our research efforts on the study of a secreted, Frizzled-related protein (sFRP-1) that is thought to have an important role in embryonic development and perhaps neoplasia. Several collaborative studies with recombinant sFRP-1 and soluble, biologically active Wnt-3a are broadening our understanding of sFRP biological activity. In a rat embryonic kidney organ culture, sFRP-1 blocked tubulogenesis presumably by inhibiting Wnt-4 activity. Recent work with other recombinant sFRP family members indicates differences in their biological activities and functions. Mapping of the disulfide bonding pattern of sFRP-1 has provided insights about Frizzled homology and the netrin module, a domain present in the carboxy-terminal region of sFRPs and other proteins. Peptide phage display analysis has identified novel binding motifs for sFRP-1. Collaborative studies have yielded new information about the activity of keratinocyte growth factor (KGF or FGF-7). Investigations have revealed a role for KGF/KGFR signaling in thymus development and T cell maturation, and explored the mechanisms responsible for KGF's ability to ameliorate the impact of graft versus host disease associated with bone marrow transplantation. Research with individual domains of hepatocyte growth factor (HGF) demonstrated that binding of heparan sulfate to Met, the HGF tyrosine kinase receptor, facilitates signaling.

在过去的一年中，我们继续把我们的研究工作集中在一种分泌的卷曲相关蛋白（sFRP-1）的研究上，这种蛋白被认为在胚胎发育和肿瘤形成中起重要作用。重组sFRP-1和可溶性生物活性Wnt-3a的几项合作研究拓宽了我们对sFRP生物活性的理解。在大鼠胚胎肾器官培养中，sFRP-1可能通过抑制Wnt-4活性来阻断肾小管形成。最近与其他重组sFRP家族成员的研究表明，它们的生物活性和功能存在差异。sFRP-1的二硫键模式的映射提供了关于卷曲同源性和netrin模块（存在于sFRP和其他蛋白质的羧基末端区域中的结构域）的见解。肽噬菌体展示分析已经鉴定了sFRP-1的新型结合基序。 合作研究已经产生了关于角质细胞生长因子（KGF或FGF-7）活性的新信息。研究揭示了KGF/KGFR信号传导在胸腺发育和T细胞成熟中的作用，并探索了KGF改善与骨髓移植相关的移植物抗宿主病影响的机制。对肝细胞生长因子（HGF）单个结构域的研究表明，硫酸乙酰肝素与HGF酪氨酸激酶受体Met的结合促进信号传导。