1,721,016 research outputs found
Molecular mechanisms that desensitize metabotropic glutamate receptor signaling: An overview
No full textThe purpose of the present article is to review our actual knowledge on the desensitization of metabotropic glutamate receptors based on the literature available so far, with the attempt to emphasize all converging data and to give a possible explanation to those evidences that still remain controversial. 1. We review our knowledge on the regulation of mGlu receptors based on the available literature 2. We report converging data and we comment on issues that still remain controversial. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. (c) 2012 Elsevier Ltd. All rights reserved.he purpose of the present article is to review our actual knowledge on the desensitization of metabotropic glutamate receptors based on the literature available so far, with the attempt to emphasize all converging data and to give a possible explanation to those evidences that still remain controversial. 1. We review our knowledge on the regulation of mGlu receptors based on the available literature 2. We report converging data and we comment on issues that still remain controversial. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'
Analysis of differential modulatory activities of GRK2 and GRK4 on G-alpha-q-coupled receptor signaling
No full textSelective regulation of G protein-coupled receptor-mediated signaling by G protein-coupled receptor kinase 2 in FRTL-5 cells: Analysis of thyrotropin, alpha(1B)-adrenergic, and A(1) adenosine receptor-mediated responses
No full textG protein-coupled receptor kinases (GRKs) play a key role in the process of receptor homologous desensitization. In the present study, we address the question of whether a variety of receptors coupled to different G protein subtypes and naturally expressed on the same cell are selectively regulated by GRK2. The signaling stimulated by thyrotropin (TSH), a1B-adrenergic, and A1 adenosine receptors was studied in FRTL-5 cells permanently transfected to overexpress GRK2 and GRK2-K220R, a kinase dead GRK dominant negative mutant. In FRTL-5 overexpressing GRK2, TSH-induced cyclic AMP response was attenuated, indicating that TSH receptor is desensitized by this kinase. Consistently, FRTL-5 cells overexpressing GRK2- K220R show increased TSH-induced cyclic AMP response, demonstrating that this receptor is under tonic control by GRK. Unlike TSH receptor, a1B-adrenergic receptor response was unaffected in FRTL-5 overexpressing GRK2 and GRK2-K220R. When A1 adenosine receptors were stimulated, Gia-mediated cyclic AMP inhibition was totally unaffected by overexpression of either GRK2 or GRK2-K220R. By contrast, Gbg-mediated response (activation of mitogen-activated protein kinases) was efficiently desensitized by GRK2 but was unaffected by GRK2- K220R overexpression. The present study documents that overexpression of GRK2 results in a selective regulation of different G protein-coupled receptors expressed on the same cell and that this kinase can regulate preferentially only one of the different pathways activated by the same receptor. The preferential regulation of the A1 adenosine receptor-stimulated mitogen-activated protein kinases by GRK2 indicates that this kinase can have additional regulatory effects on Gbg-stimulated pathways, possibly through direct binding and regulation of the receptor-Gbg complex
GRK2 and beta-arrestin 1 as negative regulators of thyrotropin receptor-stimulated response.
No full textG protein-coupled receptors: Heterologous regulation of homologous desensitization and its implications
No full textTwo patterns of rapid desensitization have been characterized for G protein-coupled receptn:d: homologous desensitizeton, which mainly involves G protein-coupled receptor kineses and arrestins, and heterologous desensitization, which mainly involves protein kinases A IPKA) and C (PKC). In this review, Tsu T&en Chuang and colleagues discuss evidence to show that PKA and PKC can modify the functional state of the G protein-coupled receptor kinases/arrestin homologous desensitization machinery, providing a novel level of cross-talk in signal transduction. Studies on regulation of G protein-coupled receptor kinases and arrestins confirm that the functional state of this machinery may have important consequences far cellular responsiveness and may represent new targets for therapeutic strategies
Regulation of G-protein-coupled receptor kinase subtypes by calcium sensor proteins.
Full text linkThe process of G-protein-coupled receptor
(GPCR) homologous desensitization is intrinsically
related to the function of a class of S/T kinases
named G-protein-coupled receptor kinases
(GRK). GRK family is so far composed of six cloned
members, named GRK1 to 6, which are classified into
three subfamilies: GRK1 is alone in the first (rhodopsin
kinase subfamily), GRK2 and 3 form the second
[b-adrenergic receptor kinase (bARK) subfamily],
and GRK4, 5, and 6 constitute the third (GRK4 subfamily).
Recent studies from different laboratories
have demonstrated that different calcium sensor proteins
(CSP) can selectively regulate the activity of
GRK subtypes. In the presence of calcium, rhodopsin
kinase (GRK1) is inhibited by the photoreceptor-specific
CSP recoverin through direct binding. Several
other recoverin homologues (including NCS 1, VILIP
1, and hippocalcin) are also able to inhibit GRK1 in
a calcium-dependent manner. The ubiquitous calcium
binding protein calmodulin (CaM) can inhibit
GRK5 with a high affinity (IC50 40–50 nM). A direct
interaction between GRK5 and Ca2//CaM was documented
and this binding did not influence the catalytic
activity of the kinase, but rather reduced GRK5
binding to the membrane. These studies suggest that
CSP act as functional analogs in mediating the regulation
of different GRK subtypes by Ca2/. This mechanism,
however, is highly selective with respect to the
GRK subtypes: GRK1, but not GRK2 and GRK5, is
regulated by recoverin and other NCS, but GRK4, 5,
and 6, which belong to the GRK4 subfamily are potently
inhibited by CaM, which has little or no effect
on members of other GRK subfamilies. Calcium-dependent
inhibition of rhodopsin kinase by recoverin
represents one of the mechanisms that control adaptation
to light. For the other GPCR, CSP-GRK interaction
provides a feedback mechanism that can
modulate homologous desensitization of these receptors
Viral Infection for GPCR Expression in Eukaryotic Cells
No full textThis chapter describes the protocol for the preparation of recombinant adenoviruses and infection of target cells to transiently express G protein-coupled receptors (GPCRs) or other proteins of interest. Adenoviruses are non-enveloped viruses containing a linear double-stranded DNA genome. Their life cycle does not normally involve integration into the host genome, rather they replicate as episomal -elements in the nucleus of the host cell, and consequently there is no risk of insertional mutagenesis. Up to 30 kb out of the 35 kb of the wild-type adenovirus genome can be replaced by foreign DNA. Adenoviral vectors are very efficient in transducing target cells in vitro and in vivo and can be produced at high titers (>10 11/mL). The viral infection has a number of useful features: (1) the efficiency of gene transduction is very high (up to 100% in sensitive cells); (2) the infection is easy and does not physically alter the cell membrane for gene transduction; (3) it is possible to infect cells that are resistant to transfection with plasmids (including nondividing cells); and (4) the viral vectors can be used for infection in vivo (including gene therapy) and can potentially be targeted cell-specifically
Differential regulation of membrane bound and soluble ICAM 1 in human endothelium and blood mononuclear cells: effects of interferon beta-1a
No full textInvolvement of dopamine receptors and beta-arrestin in metamphetamine-induced inclusions formation in pc12 cells.
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