Robert J. Lefkowitz

Bio: Robert J. Lefkowitz is an academic researcher from Howard Hughes Medical Institute. The author has contributed to research in topics: Receptor & G protein-coupled receptor. The author has an hindex of 214, co-authored 860 publications receiving 147995 citations. Previous affiliations of Robert J. Lefkowitz include University of Nice Sophia Antipolis & University of Stuttgart.

Membrane-Bound Hormone Receptors

Abstract: Receptors are those cellular structures with which biologically active hormones and drugs first interact. Physiologically these receptors perform two essential functions. The first is that of recognition of a particular biologically active chemical structure presumably by some complimentarity in the structure of the hormone or drug and the receptor itself. This recognition is effected by specific binding of the hormone or drug to the cellular receptor structures. The second function of these receptors is that of activation of biological processes. This may be effected through a stimulation of an enzyme activity, a change in the membrane conductance for a specific ion, etc. For certain hormones, e.g., the steroid hormones, the receptors appear to be cytoplasmic in location (Baulieu et al., 1971). For many other hormones and drugs, however, the receptor structures appear to be located within the plasma membranes of the responsive target cells. This chapter will be confined to the latter class of hormone receptors.

Chapter 23. Recent Developments in Adrenergic Receptor Research

Abstract: Publisher Summary Virtually all the physiological effects of catecholamines, generally termed adrenergic effects, could be classified as being of the two major types. These two types of responses are termed as “α”- and “β”-adrenergic, respectively, and hypothesized that they were mediated by two distinct types of adrenergic receptors, α- and β-adrenergic receptors. The two receptor types were distinguished by their characteristic potency series for agonist drugs. A variety of radioactively labelled ligands, both agonists and antagonists, have been developed and applied to successful study of α- and β-adrenergic binding sites in a wide variety of tissues from a wide variety of species. Research in this area has been the subject of a number of excellent and extensive reviews in the past few years. Subsequent to the classification of adrenergic receptors into α- and β- types by Ahlquist, it became clear that there were at least two major subtypes of each of these receptors. Subtypes of α-adrenergic receptors also exist, and here the situation is somewhat more complex because there is a much greater physiological distinction between these two subtypes than is the case for the β-adrenergic receptor subtypes.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

Abstract: Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression Here we investigate the requirements for structure and delivery of the interfering RNA To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference The effects of this interference were evident in both the injected animals and their progeny Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Abstract: The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)