Investigation of a secreted, Frizzled-related protein (FRP) is a major focus of current research. Frizzled proteins recently were shown to function as receptors for Wnt signaling molecules. We have now established that FRP can antagonize Wnt- dependent duplication of the dorsal axis in early Xenopus embryos. Fluorescent in situ hybridization (FISH) identified the frp locus at chromosome 8p11.1-12, a site where loss of heterozygosity has been observed in a variety of human malignancies. Thus, efforts are underway to determine whether frp mutations or deletions are present in tumor specimens, consistent with a potential role for FRP as a tumor suppressor. Ongoing structure-function analysis of HGF/SF has benefited from prokaryotic expression of various truncated derivatives, including HGF/NK1, HGF/NK2, the first kringle and the amino-terminal (N) domain. NMR structure analysis of the N domain is in an advanced stage. A study was completed that demonstrated increased expression of HGF/SF in the brain of patients with Alzheimer's disease; HGF/SF protein is found in astrocytes and microglia, rather than in the neurofibrillary tangle, suggesting that HGF/SF is produced in reaction to the underlying lesion associated with this disorder. KGF expression was observed in blood vessels in vivo and in vascular smooth muscle cells in vitro, although transcripts encoding KGF tyrosine kinase receptors were not detected in vessels, vascular smooth muscle or endothelial cells. This result suggested that KGF might have activity on cells in the circulatory system, although the precise target and the nature of the receptor remain obscure. FISH analysis revealed that a portion of the kgf gene was amplified and dispersed among many chromosomes in discrete steps during the evolution of great apes and humans. The pattern of distribution of kgf-like sequences suggested that alphoid DNA was involved in their amplification and dispersion, emphasizing the likely importance of alphoid DNA in genetic recombination events. Titled changed from Characterization of Epithelial Cell Mitogens/Receptors and Analysis of the Frizzled-Related Protein
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