Author
Robert J. Lefkowitz
Other affiliations: University of Nice Sophia Antipolis, University of Stuttgart, Laboratory of Molecular Biology ...read more
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 published on a yearly basis
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TL;DR: A few selected areas of active research where radioligand binding techinques have been applied to the study of adrenergic receptors in the heart are discussed.
Abstract: Introduction Catecholamines, acting through alphaand beta-adrenergic receptors, modulate a variety of physiological responses in the heart. Most impor tantly catecholamines increase the rate and force of cardiac contraction. These actions occur mainly as a consequence of the binding of the endoge nous substances norepinephrine and epinephrine to specific adrenergic receptors on the plasma membrane of cells in the heart. Whereas the effects of sympathetic nervous stimulation on the heart have been examined for many years (reviewed in 57), oIlly recently has it become possible to mea sure directly the properties of the receptors for catecholamines in the heart. Here we discuss a few selected areas of active research where radioligand binding techinques have been applied to the study of adrenergic receptors in the heart.
74 citations
TL;DR: Pretreatment of intact frog erythrocytes with TPA produces approximately two- to threefold increases in basal, guanine nucleotide-, prostaglandin E1-, forskolin-, NaF-, and MnCl2-stimulated adenylate cyclase activities in frog ERYthrocyte membranes.
74 citations
TL;DR: Unlike beta(2)AR overexpression, basal contractility was increased by betaARK1 inhibitor expression without increasing ischemic injury, thus implicating a safer potential therapy for heart failure.
Abstract: —Cardiac β2-adrenergic receptor (β2AR) overexpression is a potential contractile therapy for heart failure. Cardiac contractility was elevated in mice overexpressing β2ARs (TG4s) with no adverse effects under normal conditions. To assess the consequences of β2AR overexpression during ischemia, perfused hearts from TG4 and wild-type mice were subjected to 20-minute ischemia and 40-minute reperfusion. During ischemia, ATP and pH fell lower in TG4 hearts than wild type. Ischemic injury was greater in TG4 hearts, as indicated by lower postischemic recoveries of contractile function, ATP, and phosphocreatine. Because β2ARs, unlike β1ARs, couple to Gi as well as Gs, we pretreated mice with the Gi inhibitor pertussis toxin (PTX). PTX treatment increased basal contractility in TG4 hearts and abolished the contractile resistance to isoproterenol. During ischemia, ATP fell lower in TG4+PTX than in TG4 hearts. Recoveries of contractile function and ATP were lower in TG4+PTX than in TG4 hearts. We also studie...
73 citations
TL;DR: The findings introduce the use of the biosensor diacylglycerol reporter as a powerful means for studying Gq-coupled receptor desensitization and document that, at the levels of receptor overexpression commonly used in such studies, the properties of the desensItization process are markedly perturbed and do not reflect normal cellular physiology.
73 citations
TL;DR: Of the inhibitors tested EDTA and EGTA were the most active in preventing appearance of multiple labelled peptides suggesting that metal-dependent proteolysis may be involved in the generation of apparent receptor peptide heterogeneity.
72 citations
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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
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
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
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
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