Identification of an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid

Dua, Harminder S.; Reyes, Patricio F.; Barrett, Jeffrey; Abrams, Michael S.; Schwarting, Roland; Craft, Cheryl M.; Donoso, Larry A.

doi:10.1038/eye.1992.128

Cited by 5 publications

(2 citation statements)

References 23 publications

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“…Several anti-arrestin mAbs have revealed extensive cross-reactivity with arrestin-like molecules, in and out of the eye. [54][55][56][57] Furthermore, there is thymic expression of arrestinlike mRNAs, 58 many of which contain close analogues of the minimal 'M' peptide and other known pathogenic peptides of arrestin. The M peptide is familiar as the first identified uveitogenic epitope, 59 and is one of the most conserved sequences in the arrestin family.…”

Section: Complicating Factorsmentioning

confidence: 99%

Immune privilege in the retina

Gregerson¹

1998

Ocular Immunology and Inflammation

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As new Ag-specific and non-Ag-specific mechanisms contributing to ocular immune privilege are revealed, the relevance of old paradigms properly comes into question. My lab has a particular interest in the immune privilege of the retina. While the presence of active mechanisms of tolerance, such as immune deviation, is now well-established, we propose that sequestration provides the first line of immune privilege in the retina. When it fails, active, inducible mechanisms provide backup to protect the integrity of the retina and vision. Some of the observations that led to our hypotheses and their supporting experiments are discussed below.

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Section: Complicating Factorsmentioning

confidence: 99%

Immune privilege in the retina

Gregerson¹

1998

Ocular Immunology and Inflammation

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“…We tested each component of the reactions used in the preceding experiments and also brain G␤␥ using F4C1, a monoclonal antibody that recognizes the amino-terminal epitope DGVVLVD (21). This epitope is common to bovine and murine arrestin, ␤-arrestin1 and ␤-arrestin2 (35,36).…”

Section: Urea-extracted Membranes Do Not Contain Arrestin-like Reactimentioning

confidence: 99%

Phosphorylation Uncouples the Gastrin-releasing Peptide Receptor from Gq

Kroog¹,

Jian²,

Chen³

et al. 1999

Journal of Biological Chemistry

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Previous work on the desensitization of G proteincoupled receptors has focused on the role of arrestin binding following receptor phosphorylation. We have examined the hypothesis that phosphorylation alone contributes to desensitization. In this study we demonstrate that for the G q -coupled gastrin-releasing peptide receptor (GRP-R), phosphorylation by GRK2 to a stoichiometry of ϳ1 mol PO 4 /mol GRP-R is sufficient in the absence of arrestin to reduce the rate of receptor catalyzed G protein activation by approximately 80%. Furthermore, GRP-Rs exposed in vivo to agonist are rapidly phosphorylated to a similar stoichiometry and are desensitized to a similar degree. Finally, the molecular mechanism for both in vitro GRK2-induced and in vivo agonist-induced desensitization is primarily a decrease in the maximum velocity (V max ) for the catalysis of guanine nucleotide exchange by the GRP-R rather than a change in the affinity of the receptor for the ␣ q or ␤␥ subunits. Based on these results, we suggest that, for some G protein-coupled receptors, phosphorylation has a role in desensitization that is independent of arrestin.Bombesin-like peptides elicit a variety of effects including mitogenesis, hormone secretion, and modulation of neuron firing rate (1). These effects are transduced through a family of G protein-coupled receptors (GPCRs) 1 including the gastrin-releasing peptide receptor (GRP-R) (2, 3). An agonist-activated GPCR catalyzes the exchange of guanine nucleotide on the ␣ subunit of a heterotrimeric G protein leading to the formation of G␣-GTP. The subsequent dissociation of the heterotrimeric G protein leads to stimulation of signal transduction cascades mediated by the free G␣-GTP and G␤␥ subunits (4). In the bombesin receptor family, the activated GRP-R catalyzes guanine nucleotide exchange on G␣ q (5) to activate effectors including phospholipase C-␤ (3).Mechanisms to attenuate receptor signaling have evolved that limit the amplitude and/or duration of the signal transduction cascade(s) and are collectively referred to as "desensitization." At the molecular level, desensitization may result from the degradation of ligand, from changes in receptor availability or activity, or from changes in the availability or activity of downstream effector molecules (6). Rhodopsin, which signals through transducin (G t ), and the ␤ 2 -adrenergic receptor (␤ 2 AR), which signals through G s , have been the most extensively studied GPCRs. In both cases, rapid agonist-induced receptor phosphorylation along with subsequent binding of an arrestin to the receptor play critical roles in receptor deactivation (7,8). Many other GPCRs are also known to be rapidly phosphorylated after addition of agonist (9, 10), including the GRP-R (11). Two classes of protein kinase have been implicated in agonist-induced GPCR phosphorylation: 1) the second messenger-dependent protein kinases A and C and 2) the second messenger independent kinases, called G protein-coupled receptor kinases (GRKs), including rhodopsin kinase (RK or GRK1) an...

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Immunodetection of an arrestin-like protein in human retinal pigment epithelium

Reising

Kennedy

Getz

et al. 1996

Current Eye Research

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The goal of this study was to determine if an arrestin/S-antigen-like protein is produced by human retinal pigment epithelial (HRPE) cells maintained in tissue culture. Arrestin immunoreactivity was examined in fixed, monolayer cultures of HRPE and on immunoblots of SDS-PAGE separations of whole cell lysates of HRPE using five monoclonal antibodies (mAbs A2G5, A9C6, 3C4.2, 3D1.2 and 5c6.47) that bind to different epitopes in bovine retinal S-antigen. Monolayers of HRPE cells showed immunoreactivity with four of the mAbs though the relative staining intensity varied among mAbs and donors. For example, mAb A2G5 which historically shows very limited crossreactivity among species, reacted strongly with cells from one donor, moderately with cells from a second donor and only weakly with other donor cultures examined. mAb 3D1.2 showed no reactivity with HRPE cells. Immunoblots of SDS-PAGE separations of whole cell lysates of HRPE established from ten different donors confirmed the presence of an arrestin-related polypeptide that comigrated with retinal arrestin. These results demonstrate the presence of an arrestin-like protein in HRPE cells which have been maintained in tissue culture. Though the function of this arrestin homologue in HRPE is not yet established, it could play a role in the downregulation of receptor and/or transport protein activity.

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Identification of an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid

Cited by 5 publications

References 23 publications

Immune privilege in the retina

Immune privilege in the retina

Phosphorylation Uncouples the Gastrin-releasing Peptide Receptor from Gq

Immunodetection of an arrestin-like protein in human retinal pigment epithelium

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