GPI-Anchored Cell-Surface Molecules Complexed to Protein Tyrosine Kinases

Stefanová, I; Hořejšı́, Václav; Ansotegui, Ignacio J.; Knapp, Walter; Stockinger, Hannes

doi:10.1126/science.1719635

Cited by 818 publications

(542 citation statements)

References 14 publications

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“…Since CD24 is localized in lipid rafts, the absence or presence of CD24 may influence membrane raft composition and thereby affect important signaling pathways within the cell (37). It has also been reported that CD24 is involved in intracellular signaling by direct binding to tyrosine kinases (38).…”

Section: Discussionmentioning

confidence: 99%

Association of a CD24 gene polymorphism with susceptibility to systemic lupus erythematosus

Sánchez¹,

Abelson²,

Sabio³

et al. 2007

Arthritis & Rheumatism

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Objective. To determine the potential role of the CD24 A57V gene polymorphism in systemic lupus erythematosus (SLE).Methods. We studied 3 cohorts of Caucasian patients and controls. The Spanish cohort included 696 SLE patients and 539 controls, the German cohort included 257 SLE patients and 317 controls, and the Swedish cohort included 310 SLE patients and 247 controls. The CD24 A57V polymorphism was genotyped by polymerase chain reaction, using a predeveloped TaqMan allele discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.Results. In the Spanish cohort there was a statistically significant difference in the distribution of the CD24 V allele between SLE patients and controls (OR 3.6 [95% CI 2.13-6.16], P < 0.0001). In addition, frequency of the CD24 V/V genotype was increased in SLE patients compared with controls (OR 3.7 [95% CI 2.16-6.34], P < 0.00001). We sought to replicate this association with SLE in a German population and a Swedish population. A similar trend was found in the German group. The CD24 V/V genotype and the CD24 V allele were more frequent in SLE patients than in controls, although this difference was not statistically significant. No differences were observed in the Swedish group. A meta-analysis of the Spanish and German cohorts demonstrated that the CD24 V allele has a risk effect in SLE patients (pooled OR 1.25 [95% CI 1.08-1.46], P ‫؍‬ 0.003). In addition, homozygosity for the CD24 V risk allele significantly increased the effect (pooled OR 2.19 [95% CI 1.50-3.22], P ‫؍‬ 0.00007).Conclusion. These findings suggest that the CD24 A57V polymorphism plays a role in susceptibility to SLE in a Spanish population.Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with a complex pathogenesis involving multiple genetic and environmental factors. The disease is characterized by enhanced autoantibody production, abnormalities of immune/inflammatory system function, and inflammation in several organs. Al-

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Section: Discussionmentioning

confidence: 99%

Association of a CD24 gene polymorphism with susceptibility to systemic lupus erythematosus

Sánchez¹,

Abelson²,

Sabio³

et al. 2007

Arthritis & Rheumatism

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“…This is thought to occur via direct protein-protein interactions between caveolins and signaling components found at the plasma membrane. In various cell types, caveolin proteins have been shown to be associated with G protein-coupled receptors, G protein subunits, tyrosine kinase receptors, various intracellular kinases, voltage-gated ion channels, ion pumps, and various second messenger molecules [42][43][44][45].…”

Section: Caveolins: Important For the Trafficking And Clustering Of Mmentioning

confidence: 99%

Caveolin proteins and estrogen signaling in the brain

Luoma

Boulware

Mermelstein

2008

Molecular and Cellular Endocrinology

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Best described outside the nervous system, caveolins are structural proteins that form caveolae, functional microdomains at the plasma membrane that cluster related signaling molecules. Caveolin associated proteins include G protein coupled receptors and G proteins, receptor tyrosine kinases, as well as protein kinases, ion channels and various other signaling enzymes. Not surprisingly, a wide array of biological disorders are thought to be rooted in caveolin dysfunction. In addition, caveolins also traffic and cluster estrogen receptors to caveolae. Interactions between the estrogen receptors ERα and ERβ with caveolins appear critical in many non-neuronal cell types, e.g. disruption of normal function may underlie many forms of breast cancer. Recent findings suggest caveolins may also play an essential role in membrane estrogen receptor function in the nervous system. Not only are they expressed in neurons and glia, but different caveolin isoforms also appear necessary to generate distinct functional signaling complexes. With membrane estrogen receptors responsible for the efficient activation of a multitude of intracellular signaling pathways, which in turn influence a wide variety of nervous system functions, caveolin proteins are poised to act as the central coordinators of these processes.

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“…By preferentially including some proteins and excluding others, lipid rafts and related membrane microdomains such as caveolae may regulate the sorting and trafficking of certain plasma membrane proteins and lipids and compartmentalize cell-signaling events (Verkade and Simons, 1997;Anderson, 1998;Brown and London, 1998;Horejsi et al, 1999). Although lipid rafts have been inferred from functional and kinetic studies of intact cells (Mays et al, 1995;Hannan and Edidin, 1996;Sheets et al, 1997;Keller and Simons, 1998), most evidence of their existence is based on differential extraction of cells with detergent (Skibbens et al, 1989;Stefanova et al, 1991;Brown and Rose, 1992;Fiedler et al, 1993;Sargiacomo et al, 1993). These studies indicate that in addition to GSL and cholesterol, lipid rafts are enriched in GPI-anchored proteins, some transmembrane proteins, and diacylated cytoplasmic proteins including Src family kinases.…”

Section: Introductionmentioning

confidence: 99%

High-Resolution FRET Microscopy of Cholera Toxin B-Subunit and GPI-anchored Proteins in Cell Plasma Membranes

Kenworthy

Petranova

Edidin

2000

MBoC

406

311

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“Lipid rafts” enriched in glycosphingolipids (GSL), GPI-anchored proteins, and cholesterol have been proposed as functional microdomains in cell membranes. However, evidence supporting their existence has been indirect and controversial. In the past year, two studies used fluorescence resonance energy transfer (FRET) microscopy to probe for the presence of lipid rafts; rafts here would be defined as membrane domains containing clustered GPI-anchored proteins at the cell surface. The results of these studies, each based on a single protein, gave conflicting views of rafts. To address the source of this discrepancy, we have now used FRET to study three different GPI-anchored proteins and a GSL endogenous to several different cell types. FRET was detected between molecules of the GSL GM1 labeled with cholera toxin B-subunit and between antibody-labeled GPI-anchored proteins, showing these raft markers are in submicrometer proximity in the plasma membrane. However, in most cases FRET correlated with the surface density of the lipid raft marker, a result inconsistent with significant clustering in microdomains. We conclude that in the plasma membrane, lipid rafts either exist only as transiently stabilized structures or, if stable, comprise at most a minor fraction of the cell surface.

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GPI-Anchored Cell-Surface Molecules Complexed to Protein Tyrosine Kinases

Cited by 818 publications

References 14 publications

Association of a CD24 gene polymorphism with susceptibility to systemic lupus erythematosus

Association of a CD24 gene polymorphism with susceptibility to systemic lupus erythematosus

Caveolin proteins and estrogen signaling in the brain

High-Resolution FRET Microscopy of Cholera Toxin B-Subunit and GPI-anchored Proteins in Cell Plasma Membranes

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