Role of β-Arrestin in Mediating Agonist-Promoted G Protein-Coupled Receptor Internalization

Ferguson, Stephen S. G.; Downey, William; Colapietro, Anne-Marie; Barak, Larry S.; Ménard, Luc; Caron, Marc G.

doi:10.1126/science.271.5247.363

Cited by 900 publications

(724 citation statements)

References 26 publications

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“…SDF-1 binding results in the internalization of CXCR4 and phosphorylation facilitates this process but is not absolutely required. In the case of ␤2-adrenergic receptors, phosphorylation by receptor kinases was shown to enhance the arrestin-dependent internalization (43). PKC activation by PMA also induced sequestration of CXCR4 which was completely dependent on the presence of cytoplasmic tail.…”

Section: Fig 4 Desensitization Of Cxcr4mentioning

confidence: 96%

Regulation of Human Chemokine Receptors CXCR4

Haribabu

Richardson

Fisher

et al. 1997

Journal of Biological Chemistry

258

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Members of the chemokine receptor family CCR5 and CXCR4 have recently been shown to be involved in the entry of human immunodeficiency virus (HIV) into target cells. Here, we investigated the regulation of CXCR4 in rat basophilic leukemia cells (RBL-2H3) stably transfected with wild type (Wt CXCR4) or a cytoplasmic tail deletion mutant (⌬Cyto CXCR4) of CXCR4. The ligand, stromal cell derived factor-1 (SDF-1) stimulated higher G-protein activation, inositol phosphate generation, and a more sustained calcium elevation in cells expressing ⌬Cyto CXCR4 relative to Wt CXCR4. SDF-1 and phorbol 12-myristate 13-acetate (PMA), but not a membrane permeable cAMP analog induced rapid phosphorylation as well as desensitization of Wt CXCR4. Phosphorylation of ⌬Cyto CXCR4 was not detected under any of these conditions. Despite lack of receptor phosphorylation, calcium mobilization by SDF-1 in ⌬Cyto CXCR4 cells was partially desensitized by prior treatment with SDF-1. Of interest, the rapid release of calcium was inhibited without affecting the sustained calcium elevation, indicating independent regulatory pathways for these processes. PMA completely inhibited phosphoinositide hydrolysis and calcium mobilization in Wt CXCR4 but only partially inhibited these responses in ⌬Cyto CXCR4. cAMP also partially inhibited these responses in both Wt CXCR4 and ⌬Cyto CXCR4. SDF-1, PMA, and cAMP caused phosphorylation of phospholipase C␤3 in Wt and ⌬Cyto CXCR4 cells. Both SDF-1 as well as PMA induced rapid internalization of Wt CXCR4. SDF-1 but not PMA induced internalization of ⌬Cyto CXCR4 albeit at reduced levels relative to Wt CXCR4. These results indicate that signaling and internalization of CXCR4 are regulated by receptor phosphorylation dependent and independent mechanisms. Desensitization of CXCR4 signaling, independent of receptor phosphorylation, appears to be a consequence of the phosphorylation of phospholipase C␤3.Chemokines are a group of proteins that mediate directed migration and activation of leukocytes (1). These have been classified into two main families, CXC or CC-chemokines. Two newly identified proteins define additional groups of C and CX3C chemokines based on the position of conserved cysteines (2, 3). Both CC and CXC chemokines bind to seven transmembrane G-protein-coupled receptors which transduce signals through heterotrimeric G-proteins (4). Several recent studies showed that chemokines play a significant role in human immunodeficiency virus (HIV-1) 1 infection and that the chemokine receptors CCR5 and CXCR4 along with CD4 act as major co-receptors for the macrophage tropic and T-cell tropic HIV-1 strains entry, respectively, into target cells (5-10). While the C-C chemokines such as MIP1␣, MIP1␤, and regulated upon activation, normal T expressed and secreted can activate CCR5 the CXC chemokine SDF-1 is the ligand for CXCR4 (11-13). Recently, CD4 independent infection by HIV-2 was shown to be mediated by CXCR4 (14). HIV-1 envelope glycoproteins interact with chemokine receptors in a CD4-dependent and in one case...

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Section: Fig 4 Desensitization Of Cxcr4mentioning

confidence: 96%

Regulation of Human Chemokine Receptors CXCR4

Haribabu

Richardson

Fisher

et al. 1997

Journal of Biological Chemistry

258

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“…Desensitization of GPCR-mediated signal transduction is mediated through an impairment of the receptor's ability to activate its corresponding G-protein and is carried out principally through the combined activity of two classes of proteins; G-protein-coupled serine/threonine receptor kinases (GRKs) and arrestins (reviewed in Freedman and Lefkowitz, 1996). While the role of GRKs and arrestins in desensitization pathways has been well established, it is likely that they are also intimately involved in GPCR internalization (sequestration), which is an integral component of GPCR resensitization (Ferguson et al, 1996). In D. melanogaster, mutations in two visual system arrestin genes (arr1 and arr2) have been shown to inactivate rhodopsin in vivo (Dolph et al, 1993).…”

Section: Olfactory Mechanismsmentioning

confidence: 99%

Olfactory regulation of mosquito–host interactions

Zwiebel

Takken

2004

Insect Biochemistry and Molecular Biology

264

161

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Mosquitoes that act as disease vectors rely upon olfactory cues to direct several important behaviors that are fundamentally involved in establishing their overall vectorial capacity. Of these, the propensity to select humans for blood feeding is arguably the most important of these olfactory driven behaviors in so far as it significantly contributes to the ability of these mosquitoes to transmit pathogens that cause diseases such as dengue, yellow fever and most significantly human malaria. Here, we review significant advances in behavioral, physiological and molecular investigations into mosquito host preference, with a particular emphasis on studies that have emerged in the post-genomic era that seek to combine these approaches.

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“…Recent evidence suggests that arrestins are involved in agonistmediated receptor endocytosis [179]. Overexpression of β-arrestin-1\2 rescues agonist-mediated internalization of an internalization-defective mutant of the β # -AR, and overexpression of a dominant-negative β-arrestin mutant inhibits agonist-induced internalization of the β # -AR.…”

Section: Role Of Arrestins In Receptor Endocytosismentioning

confidence: 99%

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

Böhm

Grady

Bunnett

1997

Biochemical Journal

474

322

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The large and functionally diverse group of G-protein-coupled receptors includes receptors for many different signalling molecules, including peptide and non-peptide hormones and neurotransmitters, chemokines, prostanoids and proteinases. Their principal function is to transmit information about the extracellular environment to the interior of the cell by interacting with the heterotrimeric G-proteins, and they thereby participate in many aspects of regulation. Cellular responses to agonists of these receptors are usually rapidly attenuated. Mechanisms of signal attenuation include removal of agonists from the extracellular fluid, receptor desensitization, endocytosis and downregulation. Agonists are removed by dilution, uptake by transporters and enzymic degradation. Receptor desensitization is mediated by receptor phosphorylation by G-protein receptor kinases and second-messenger kinases, interaction of phosphorylated receptors with arrestins and receptor uncoupling from

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Role of β-Arrestin in Mediating Agonist-Promoted G Protein-Coupled Receptor Internalization

Cited by 900 publications

References 26 publications

Regulation of Human Chemokine Receptors CXCR4

Regulation of Human Chemokine Receptors CXCR4

Olfactory regulation of mosquito–host interactions

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

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