ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2227209

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

G proteins are central to the transduction of many receptor signals. I review the “firsts” that have led to our current knowledge and delineate some of the issues being investigated in several laboratories worldwide.— Birnbaumer, L. Transduction of receptor signal into modulation of effector activity by G proteins: the first 20 years or so …FASEB J.4: 3068‐3078; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2172060

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

In this review we describe fundamental concepts and applications of conformational energy computations, with emphasis on some recent advances and problems being investigated. The formulation of potential energy functions is described, including the nature of the intramolecular force field, the representation of interactions with the solvent, and considerations of entropy contributions. Approaches to the search for the optimal potential energy are summarized. Examples cited among applications of conformational energy computations include refinement of X‐ray crystallographic structures, the use of computations in conjunction with NMR data, prediction of the structures of proteins based on either homology or on other procedures that surmount the multiple‐minima problem, the analysis of hierarchical levels of structure and assembly, and interactions in enzyme‐substrate complexes.— Nemethy, G.; Scheraga, H. A. Theoretical studies of protein conformation by means of energy computations.FASEB J.4: 3189‐3197; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2227210

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

More than 70 lectins from leguminous plants belonging to different suborders and tribes have been isolated, mostly from seeds, and characterized to varying degrees. Although they differ in their carbohydrate specificities, they resemble each other in their physicochemical properties. They usually consist of two or four subunits (25‐30 kDa), each with one carbohydrate binding site. Interaction with carbohydrates requires tightly bound Ca2+and Mn2+(or another transition metal). The primary sequences of more than 15 legume lectins have been established by chemical or molecular genetic techniques. They exhibit remarkable homologies, with a significant number of invariant amino acid residues, among them most of those involved in metal binding. The 3‐dimensional structures of the legume lectins are similar, too, and are characterized by a high content of β‐sheets and a lack of α‐helix. The location of the metal and carbohydrate binding sites, established unequivocally in concanavalin A by high resolution X‐ray crystallography, appears to be the same in the other legume lectins. Several of the lectin genes have been cloned and expressed in heterologous systems. This opens the way for the application of molecular genetics to the investigation of the atomic structure of the carbohydrate binding sites of the lectins, and of the relationship between their structure and biological activity. The new approaches may also provide information on the mechanisms that control gene expression in plants and on the role of lectins in nature.— Sharon, N.; Lis, H. Legume lectins: a large family of homologous proteins.FASEB J.4: 3198‐3208; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2227211

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Oncogenes play a major role in the control of proliferation in animal cells. Because the growth of cell populations is regulated by the stimulatory and inhibitory growth factors in the environment, we have attempted in this review to relate the function of oncogenes to the mechanism of action of growth factors. This correlation allows a description of the cell cycle that rests on a molecular basis and in which proto‐oncogenes figure prominently as the cellular messengers of the environmental growth stimuli.— Travali, S.; Koniecki, J.; Petralia, S.; Baserga, R. Oncogenes in growth and development.FASEB J.4: 3209‐3214; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2227212

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Many intracellular pathways are set in motion by the binding of tumor necrosis factor (TNF) to its cell surface receptor. Major steps in the TNF‐mediated cytotoxicity cascade include G protein‐coupled activation of phospholipases, generation of free radicals, and damage to nuclear DNA by endonucleases. Ultimately the cells undergo apoptosis and die. Understanding how TNF initiates these pathways will facilitate the rational design of pharmaceuticals that can attenuate or potentiate the action of this important cytokine.— Larrick, J. W.; Wright, S. C. Cytotoxic mechanism of tumor necrosis factor‐α.FASEB J.4: 3215‐3223; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2172061

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

In most organisms, the pyruvate dehydrogenase complex catalyzes the pivotal irreversible reaction that leads to the consumption of glucose in the aerobic, energy‐generating pathways. A combination of biochemical and molecular biology studies have greatly expanded our understanding of the overall structural organization of this multicomponent system, delineated the locations and elucidated the functions of structural domains of the catalytic components, and revealed significant evolutionary changes. Important to this progress was the deduction of the primary amino acid sequences from cDNA clones for each of the catalytic components from several species. The greatest detail is available for the FAD‐containing dihydrolipoamide dehydrogenase component, which is the only component for which tertiary structure information has recently emerged. For the dihydrolipoamide acetyltransferase core component, a similar but species‐variable multidomain structure is established that is responsible for the distinct architectures of the inner cores, the peripheral binding of the other components, and the conveyance of reaction intermediates between distantly separated active sites. A second lipoyl‐bearing component, protein X, has been shown to play a critical role in the organization and function of the complex from many higher organisms. Although much is known about the means of effector modulation of mammalian complex activity, identification of the signal eliciting its regulation by insulin still poses an exciting challenge.— Patel, M. S.; Roche, T. E. Molecular biology and biochemistry of pyruvate dehydrogenase complexes.FASEB J.4: 3224‐3233; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2227213

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Patients with apparent mineralocorticoid excess (AME) have low or absent activity of the enzyme 11βOH steroid dehydrogenase (11SD), and inappropriately high intrarenal levels of cortisol resulting in Na+retention and hypertension. Pseudohypoaldosteronism (PHA), in contrast, is characterized by salt wasting despite hyperaldosteronemia, reflecting low or absent mineralocorticoid receptors (MR). Although AME is presumed to reflect inappropriate cortisol occupancy of MR, several features also suggest inappropriate occupancy of glucocorticoid receptors (GR). To test this possibility, we administered carbenoxolone, which is known to block 11SD, to four patients with PHA, and observed marked mineralocorticoid effects, e.g., antinatriuresis and elevated plasma bicarbonate. To further test the possibility that occupancy of renal GR may induce a classical mineralocorticoid response, we administered the highly specific glucocorticoid RU 28362 to adrenalectomized rats and showed that it has profound antinatriuretic effects. Finally, by selectively blocking MR with RU 28318 or GR with RU 38486, we have shown that corticosterone, the physiologic glucocorticoid in rats, has an antinatriuretic effect in adrenalectomized rats via either MRorGR occupancy. Previous studies have clearly shown that MR are inherently nonselective and have equivalent intrinsic affinity for aldosterone, corticosterone, and cortisol. The present studies suggest that this non‐selectivity includes the nuclear response element to which either MR or GR may bind to elicit a mineralocorticoid effect, and further underscore the importance of the enzyme 11SD in the specific mineralocorticoid action of aldosterone.— Funder, J. W.; Pearce, P. T.; Myles, K.; Roy, L. P. Apparent mineralocorticoid excess, pseudohypoaldosteronism, and urinary electrolyte excretion: toward a redefinition of mineralocorticoid action.FASEB J.4: 3234‐3238; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2172062

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

Paraquat, which mediates increased O2−production withinEscherichia coli, inhibits growth without causing cell death in a minimal medium, whereas it allows growth while decreasing viability in a rich medium. Agents or conditions that inhibit growth in the paraquat‐containing rich medium prevent this loss of viability. Antibiotics, chelating agents, nutritional paucity, and excess paraquat all acted this way. NaCl added to 0.2 M to the plates used for enumeration after paraquat exposure did not significantly decrease viable cell counts, although it did so after exposure to a cationic detergent. DNA, rather than cell membranes, thus seems to be a more likely target for the oxygen‐derived free radicals engendered by the cycles of enzymatic reduction and autoxidation of paraquat. Inhibition of growth decreases the likelihood that DNA replication will precede DNA repair. Investigators seeking to evaluate the bactericidal actions of paraquat under a variety of conditions will need to be cognizant of this need for growth.— Minakami, H.; Fridovich, I. Relationship between growth ofEscherichia coliand susceptibility to the lethal effect of paraquat.FASEB J.4: 3239‐3244; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2172063

出版商:Wiley    

年代:1990

数据来源: WILEY

摘要:

An established line of human epidermal keratinocytes was permanently transformed by transfection with plasmid vectors bearing the human growth hormone gene under the control of two different promoters. Suitable selection permitted the isolation of clones secreting abundant growth hormone in culture. When such cultures were grafted to athymic mice, human growth hormone could be detected in the blood of the mice at concentrations in the physiological range for more than 4 weeks. Retrograde transfer from epithelial cells should be studied further as a possible means of introducing exogenous gene products into the circulation of humans.— Teumer, J.; Lindahl, A.; Green, H. Human growth hormone in the blood of athymic mice grafted with cultures of hormone‐secreting human keratinocytes.FASEB J.4: 3245‐3250; 1990.

ISSN:0892-6638    

DOI:10.1096/fasebj.4.14.2227214

出版商:Wiley    

年代:1990

数据来源: WILEY