Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product

THE superfamily of low molecular mass GTP-binding proteins, for which the ras proteins are prototypes, has been implicated in the regulation of diverse biological activities including protein trafficking, secretion, and cell growth and differentiation. One member of this family, CDC42Hs (originally referred to as Gp or G25K), seems to be the human homologue of the Saccharomyces cerevisiae cell-division-cycle protein, CDC42Sc. A second S. cerevisiae protein, CDC24, which is known from complementation studies to act with CDC42Sc to regulate the development of normal cell shape and the selection of nonrandom budding sites in yeast, contains a region with sequence similarity to the dbl oncogene product. Here we show that dbl specifically catalyses the dissociation of GDP from CDC42Hs and thereby qualifies as a highly selective guanine nucleotide exchange factor for the GTP-binding protein. Although guanine nucleotide exchange activities have been previously described for other members of the Ras-related GTP-binding protein family, this is the first demonstration, to our knowledge, of the involvement of a human oncogenic protein in catalysing exchange activity.     

Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis

Leukotrienes, the biologically active metabolites of arachidonic acid, have been implicated in a variety of inflammatory responses, including asthma, arthritis and psoriasis. Recently a compound, MK-886, has been described that blocks the synthesis of leukotrienes in intact activated leukocytes, but has little or no effect on enzymes involved in leukotriene synthesis, including 5-lipoxygenase, in cell-free systems. A membrane protein with a high affinity for MK-886 and possibly representing the cellular target for MK-886 has been isolated from rat and human leukocytes. Here, we report the isolation of a complementary DNA clone encoding the MK-886-binding protein. We also demonstrate that the expression of both the MK-886-binding protein and 5-lipoxygenase is necessary for leukotriene synthesis in intact cells. Because the MK-886-binding protein seems to play a part in activating this enzyme in cells, it is termed the five-lipoxygenase activating protein (FLAP).     

Diketopiperazines from fermentations: Metabolites,artifacts, or both

Zusammenfassung Es wird gezeigt, dass Diketopiperazine, insbesonderel-Leucyl-l-prolin-anhydrid, eher aus dem Medium stammende Artefakte als echte mikrobielle Stoffwechselprodukte sind.     

The in vivo activity of combinations of 5-azacytidine and cytidine on leukemia L-1210

Zusammenfassung Cytidin- oder Uridinzufuhr, bei an Leukämie L-1210 erkrankten Mäusen entweder 1 h vor oder gleichzeitig mit 5-Azacytidin verabreicht, bewirkt eine Herabsetzung der Toxizität von 5-Azacytidin, die sich in der Gewichtsveränderung und Verlängerung der Lebenszeit zeigt. Aufgrund der gefundenen zeitlichen Verhältnisse wird die Hypothese aufgestellt, dass Cytidin oder Uridin nur dann wirksam werden, wenn der Ort der metabolischen Vorgänge gleichzeitig mit 5-Azacytidin erreicht wird.     

A nonenzymic oxygen uptake and its implications in the assay of 4-hydroxyphenylpyruvate dioxygenase by an oxygen electrode

Summary The oxygen electrode provides a rapid, convenient assay for 4-hydroxyphenylpyruvate dioxygenase. However, due to the occurrence of a nonenzymic oxygen consumption when reducing agents were mixed witha,a-dipyridyl, its use is restricted to species which do not require reducing agents or necessitates the addition of catalase to the reaction mixture.