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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.


Papers
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Journal ArticleDOI
TL;DR: It is suggested that the peripheral PMNLs from psoriatic patients are normal, but the sera of Psoriatic arthritis patients has more chemokinetic activity forPMNLs than does normal serum.

38 citations

Journal ArticleDOI
TL;DR: The β 1 and β 2 -adrenergic receptor subtypes are biochemically and functionally similar and mediate the catecholamine-induced activation of adenylyl cyclase through the GTP-binding protein G s.

38 citations

Journal ArticleDOI
TL;DR: The idea of receptors has fascinated scientists for more than a century and has certainly fascinated me and Brian throughout the entirety of the authors' research careers and despite the very central role that the study of receptors plays in biomedical research today, it is only in the last thirty years or so that there has been any general acceptance they even exist.
Abstract: The idea of receptors has fascinated scientists for more than a century and has certainly fascinated me and Brian throughout the entirety of our research careers. Today we know that the G protein coupled receptors, also known as seven transmembrane receptors, represent by far the largest, most versatile and most ubiquitous of the several families of plasma membrane receptors. They comprise almost a thousand genes which regulate virtually all known physiological processes in humans including the sensory modalities of vision, taste and smell. Moreover, these receptors are the targets for drugs accounting for more than half of all prescription drug sales in the world (1). Despite the very central role that the study of receptors plays in biomedical research today, it is only in the last thirty years or so that there has been any general acceptance they even exist. Prior to that time, the notion of cellular receptors was highly controversial and associated with a great deal of skepticism. Perhaps the earliest explicit assertion concerning the existence of receptors was made by the British pharmacologist, J.N. Langley. In 1905 he wrote the following: “So we may suppose that in all cells two constituents at least are to be distinguished. The chief substance which is concerned with the chief function of the cell as contraction and secretion and receptive substances which are acted upon by chemical bodies and in certain cases by nervous stimuli. The receptive

36 citations

Journal ArticleDOI
TL;DR: A cDNA encoding bovine βARK has been isolated from a retinal cDNA library and it is revealed that the human βARK locus segregated with the long arm of chromosome 11, centromeric to 11q13.

36 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组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�ly.
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。

18,940 citations

Journal ArticleDOI
19 Feb 1998-Nature
TL;DR: To their surprise, it was found that double-stranded RNA was substantially more effective at producing interference than was either strand individually, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
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

15,374 citations

Journal ArticleDOI
TL;DR: This approach provides two major advantages compared with other available methods: it uses an exact mathematical model of the ligand-binding system, thereby avoiding the possible biases introduced by several commonly used approximations and it uses a statistically valid, appropriately weighted least-squares curve-fitting algorithm with objective measurement of goodness of fit.

8,717 citations

Journal ArticleDOI
13 Oct 2000-Cell
TL;DR: Understanding of the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases.

7,056 citations

Journal ArticleDOI
TL;DR: This review considers recent findings regarding GC action and generates criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stress-response or, as an additional category, is preparative for a subsequent stressor.
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)

6,707 citations