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.
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