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991.
L A Tong A M de Vos M V Milburn J Jancarik S Noguchi S Nishimura K Miura E Ohtsuka S H Kim 《Nature》1989,337(6202):90-93
One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene. To understand the structural reasons behind cell transformation arising from this single amino acid substitution, we have determined the crystal structure of the GDP-bound form of the mutant protein, p21(Val-12), encoded by this oncogene. We report here the overall structure of p21(Val-12) at 2.2 A resolution and compare it with the structure of the normal c-Ha-ras protein. One of the major differences is that the loop of the transforming ras protein that binds the beta-phosphate of the guanine nucleotide is enlarged. Such a change in the 'catalytic site' conformation could explain the reduced GTPase activity of the mutant, which keeps the protein in the GTP bound 'signal on' state for a prolonged period time, ultimately causing cell transformation. 相似文献
992.
993.
This issue of EXPERIENTIA on ‘Developments in Biotechnology’ is dedicated to Professor Armin Fiechter who celebrated his 65th birthday in October. He is one of the most eminent promoters of biotechnology in Switzerland and he was instrumental in establishing the Institute for Biotechnology at ETH in 1982 of which he is still director. By pioneering the combination of fundamental and applied aspects he has greatly influenced the advancement of biotechnology in teaching and research in Switzerland. Distinguished scientists from various countries were invited to contribute to this special issue of EXPERIENTIA to review aspects of yeast physiology, process optimization and control, analytics, and applications. We are well aware that the articles presented here are only a narrow selection of the current activities in biotechnology but since Professor Fiechter has devoted most of his scientific career to research on yeast physiology, process development and instrumentation it is appropriate to focus this issue on these aspects. We thank all the authors who have contributed to mark this special event. Professor Fiechter continues to actively stimulate progress in biotechnology with a still lively awareness of future developments. May he continue to persue his objectives and, together with Mrs. Fiechter, enjoy the time to come. 相似文献
994.
Summary Male Fischer F-344 rats were given ethanol in the drinking water and/or by single oral administration. Following this, the animals received p.o. 100 ng/kg of the hepatocarcinogen [3H]aflatoxin B1 (AFB1). 24 h later, the level of DNA-bound AFB1 was determined in the liver and was found not to be affected by any type of ethanol pretreatment. A cocarcinogenic effect of ethanol in the liver is therefore unlikely to be due to an effect on the metabolic activation and inactivation processes governing the formation of DNA-binding AFB1 metabolites.To whom correspondence should be addressed.Acknowledgment. We thank the European Science Foundation for the Toxicology Research Fellowship awarded to M.M. 相似文献
995.
Harvey (Ha-MSV) and Kirsten (Ki-MSV) murine sarcoma viruses induce tumours in animals and transform various cells in culture because of the expression of the ras oncogene product, p21 (ref. 1). Proto-oncogenes homologous with these genes are highly conserved evolutionarily and activated ras oncogenes have been detected in many human cancers. Whether c-ras oncogenes are directly responsible for human carcinogenesis is uncertain; however, it is clear that p21 mediates virus-induced transformation, although by an unknown mechanism. Epithelial and fibroblast cell lines transformed with Ha-MSV and Ki-MSV express p21 (ref. 8) and exhibit reduced adenylate cyclase activity. Like the guanine nucleotide regulatory proteins, Ns and Ni, which mediate stimulation and inhibition, respectively, of adenylate cyclase, p21 is a membrane-associated GTP binding protein, which exhibits GTPase activity. These similarities suggest that p21 and the adenylate cyclase regulatory proteins are related in cellular function, and that p21 depresses adenylate cyclase by inhibiting the activity of Ns or acting as Ni. We have therefore now examined the structural and functional similarities between p21 and Ns and Ni and find no evidence that p21 regulates adenylate cyclase activity by acting as one of these regulatory proteins. 相似文献
996.
Functions of fatty acid binding proteins 总被引:1,自引:0,他引:1
R. M. Kaikaus N. M. Bass R. K. Ockner 《Cellular and molecular life sciences : CMLS》1990,46(6):617-630
Summary Cytosolic fatty acid binding proteins (FABP) belong to a gene family of which eight members have been conclusively identified. These 14–15 kDa proteins are abundantly expressed in a highly tissue-specific manner. Although the functions of the cytosolic FABP are not clearly established, they appear to enhance the transfer of long-chain fatty acids between artificial and native lipid membranes, and also to have a stimulatory effect on a number of enzymes of fatty acid metabolism in vitro. These findings, as well as the tissue expression, ligand binding properties, ontogeny and regulation of these proteins provide a considerable body of indirect evidence supporting a broad role for the FABP in the intracellular transport and metabolism of long-chain fatty acids. The available data also support the existence of structure- and tissue-specific specialization of function among different members of the FABP gene family. Moreover, FABP may also have a possible role in the modulation of cell growth and proliferation, possibly by virtue of their affinity for ligands such as prostaglandins, leukotrienes and fatty acids, which are known to influence cell growth activity. FABP structurally unrelated to the cytosolic gene family have also been identified in the plasma membranes of several tissues (FABPpm). These proteins have not been fully characterized to date, but strong evidence suggests that they function in the transport of long-chain fatty acids across the plasma membrane. 相似文献
997.
BAHL KN 《Current science》1947,16(11):331-333
998.
Studies with isolated rat adrenocortical cells have shown that neuropeptide Y (NPY) inhibits both basal and ACTH-stimulated corticosterone secretion. These results suggest the regulatory role of NPY in corticosterone secretion from the adrenal gland, especially during stress. 相似文献
999.
1000.
M. K. Ticku 《Cellular and molecular life sciences : CMLS》1989,45(5):413-418
Summary Ethanol has a pharmacological profile similar to that of classes of drugs like benzodiazepines and barbiturates, which enhance GABAergic transmission in the mammalian CNS. Several lines of behavioral, electrophysiological and biochemical studies suggest that ethanol may bring about most of its effects by enhancing GABAergic transmission. Recently, ethanol at relevant pharmacological concentrations has been shown to enhance GABA-induced36Cl-fluxes in cultured spinal cord neurons, synaptoneurosomes and microsacs. These enhancing effects of ethanol were blocked by GABA antagonists. Ro15-4513, an azido analogue of classical BZ antagonist Ro15-1788, reversed most of the behavioral effects of ethanol and other effects involving36Cl-flux studies. The studies summarized below indicate that most of the pharmacological effects of ethanol can be related to its effects on GABAergic transmission. 相似文献