title: Catalytic lectin (leczyme) from bullfrog (Rana catesbeiana) eggs.
abstract: Catalytic lectins (leczymes) of frog eggs are sialic acid-binding lectins that have intrinsic RNase activity. They inhibit tumor cell proliferation in vitro and in vivo, although their cytotoxic mechanism remains unclear. RNase A has no tumoricidal activity. It is hypothesized that leczymes bind to cell surface sialoglycoconjugate receptors, enter the cell, and subsequently degrade RNA. In order to investigate the cytotoxic mechanism of cSBL, a leczyme from Rana catesbeiana eggs, we established cSBL-resistant clone RC-150 from mouse leukemia P388 cells. cSBL-treated P388 cells showed extensive RNA degradation over the course of 1 h, whereas cSBL-treated RC-150 cells showed no RNA degradation even over the course of 24 h. Treatment of P388 cells with cSBL led to decreased concentration of intracellular Ca2+, decreased protein kinase A activity, and increased protein kinase G activity. Incubation with cSBL decreased glutathione levels and enhanced glutathione-S-transferase (GST) activity in P388 cells, but had no effect on RC-150 cells. We conclude that cSBL-specific degradation of RNA occurs in cSBL-sensitive tumor cells, that cSBL leads to alteration of signal transduction and an intracellular protein kinase cascade reaction, and that internalized cSBL is detoxified by GST or thioltransferase. Our findings support a bifunctional model in which a leczyme is both an adhesive protein (binding to sialoglycoconjugates) and an enzyme (displaying RNnase activity).
authors.affiliation: UNIV WASHINGTON, SEATTLE, WA 98119 USA. BIOMEMBRANE INST, SEATTLE, WA 98119 USA.
authors.forename: K
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authors.lastname: Nitta
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authors.lastname: Ozaki
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authors.lastname: Tsukamoto
authors.forename: M
authors.initials: M
authors.lastname: Hosono
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authors.lastname: Ogawakonno
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authors.lastname: Kawauchi
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authors.lastname: Takayanagi
authors.forename: S
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authors.lastname: Tsuiki
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authors.lastname: Hakomori