Structure/Function of Frizzled-related protein

在过去的一年中，我们继续将研究重点放在研究一种分泌的卷曲相关蛋白（sFRP-1）上，该蛋白被认为在胚胎发育和肿瘤形成中起重要作用。一些与重组sFRP-1和可溶性生物活性Wnt-3a的合作研究正在拓宽我们对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活性来阻断小管形成。最近对其他重组sFRP家族成员的研究表明，它们的生物活性和功能存在差异。绘制sFRP-1的二硫键模式提供了对frizzledhomology和netrin模块（一个存在于sFRPs和其他蛋白质的羧基端区域的结构域）的见解。肽噬菌体展示分析已经确定了sFRP-1的新的结合基序。

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.