scholarly journals Kinase activity profiling reveals contribution of G-protein signaling modulator 2 deficiency to impaired regulatory T cell migration in rheumatoid arthritis

2021 ◽  
Vol 124 ◽  
pp. 102726
Author(s):  
Anja Meyer ◽  
Shuaifeng Yan ◽  
Viktoria Golumba-Nagy ◽  
Ruth L. Esser ◽  
Verena Barbarino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Migration ◽  
T Cell ◽  
G Protein ◽  
Regulatory T Cell ◽  
Kinase Activity ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Activity Profiling ◽  
T Cell Migration

scholarly journals RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation

2013 ◽  
Vol 305 (10) ◽  
pp. L693-L701 ◽  
Author(s):  
Jesse W. Williams ◽  
Douglas Yau ◽  
Nan Sethakorn ◽  
Jacob Kach ◽  
Eleanor B. Reed ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Migration ◽  
T Cell ◽  
Immune Responses ◽  
G Protein ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Cell Numbers ◽  
T Cell Migration

T cell migration toward sites of antigen exposure is mediated by G protein signaling and is a key function in the development of immune responses. Regulators of G protein signaling (RGS) proteins modulate G protein signaling; however, their role in the regulation of adaptive immune responses has not been thoroughly explored. Herein we demonstrated abundant expression of the Gi/Gq-specific RGS3 in activated T cells, and that diminished RGS3 expression in a T cell thymoma increased cytokine-induced migration. To examine the role of endogenous RGS3 in vivo, mice deficient in the RGS domain (RGS3ΔRGS) were generated and tested in an experimental model of asthma. Compared with littermate controls, the inflammation in the RGS3ΔRGS mice was characterized by increased T cell numbers and the striking development of perivascular lymphoid structures. Surprisingly, while innate inflammatory cells were also increased in the lungs of RGS3ΔRGS mice, eosinophil numbers and Th2 cytokine production were equivalent to control mice. In contrast, T cell numbers in the draining lymph nodes (dLN) were reduced in the RGS3ΔRGS, demonstrating a redistribution of T cells from the dLN to the lungs via increased RGS3ΔRGS T cell migration. Together these novel findings show a nonredundant role for endogenous RGS3 in controlling T cell migration in vitro and in an in vivo model of inflammation.

scholarly journals A Regulator of G Protein Signaling-containing Kinase Is Important for Chemotaxis and Multicellular Development inDictyostelium

2003 ◽  
Vol 14 (4) ◽  
pp. 1727-1743 ◽  
Author(s):  
Binggang Sun ◽  
Richard A. Firtel
Keyword(s):  
Protein Kinase ◽  
G Protein ◽  
Kinase Activity ◽  
Site Directed Mutagenesis ◽  
Membrane Localization ◽  
Pleckstrin Homology Domain ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Wild Type ◽  
Gene Encoding

We have identified a gene encoding RGS domain-containing protein kinase (RCK1), a novel regulator of G protein signaling domain-containing protein kinase. RCK1 mutant strains exhibit strong aggregation and chemotaxis defects. rck1 null cells chemotax ∼50% faster than wild-type cells, suggesting RCK1 plays a negative regulatory role in chemotaxis. Consistent with this finding, overexpression of wild-type RCK1 reduces chemotaxis speed by ∼40%. On cAMP stimulation, RCK1 transiently translocates to the membrane/cortex region with membrane localization peaking at ∼10 s, similar to the kinetics of membrane localization of the pleckstrin homology domain-containing proteins CRAC, Akt/PKB, and PhdA. RCK1 kinase activity also increases dramatically. The RCK1 kinase activity does not rapidly adapt, but decreases after the cAMP stimulus is removed. This is particularly novel considering that most other chemoattractant-activated kinases (e.g., Akt/PKB, ERK1, ERK2, and PAKa) rapidly adapt after activation. Using site-directed mutagenesis, we further show that both the RGS and kinase domains are required for RCK1 function and that RCK1 kinase activity is required for the delocalization of RCK1 from the plasma membrane. Genetic evidence suggests RCK1 function lies downstream from Gα2, the heterotrimeric G protein that couples to the cAMP chemoattractant receptors. We suggest that RCK1 might be part of an adaptation pathway that regulates aspects of chemotaxis in Dictyostelium.

scholarly journals Cutting Edge: Regulator of G Protein Signaling-1 Selectively Regulates Gut T Cell Trafficking and Colitic Potential

2011 ◽  
Vol 187 (5) ◽  
pp. 2067-2071 ◽  
Author(s):  
Deena L. Gibbons ◽  
Lucie Abeler-Dörner ◽  
Tim Raine ◽  
Il-Young Hwang ◽  
Anett Jandke ◽  
...  
Keyword(s):  
T Cell ◽  
G Protein ◽  
Cutting Edge ◽  
G Protein Signaling ◽  
Cell Trafficking ◽  
Protein Signaling ◽  
T Cell Trafficking

scholarly journals Regulation of the Epithelial Na+ Channel by the RH Domain of G Protein-coupled Receptor Kinase, GRK2, and Gαq/11

2011 ◽  
Vol 286 (22) ◽  
pp. 19259-19269 ◽  
Author(s):  
Il-Ha Lee ◽  
Sung-Hee Song ◽  
Craig R. Campbell ◽  
Sharad Kumar ◽  
David I. Cook ◽  
...  
Keyword(s):  
G Protein ◽  
Kinase Activity ◽  
Receptor Activation ◽  
Na Channel ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Α Subunits

The G protein-coupled receptor kinase (GRK2) belongs to a family of protein kinases that phosphorylates agonist-activated G protein-coupled receptors, leading to G protein-receptor uncoupling and termination of G protein signaling. GRK2 also contains a regulator of G protein signaling homology (RH) domain, which selectively interacts with α-subunits of the Gq/11 family that are released during G protein-coupled receptor activation. We have previously reported that kinase activity of GRK2 up-regulates activity of the epithelial sodium channel (ENaC) in a Na+ absorptive epithelium by blocking Nedd4-2-dependent inhibition of ENaC. In the present study, we report that GRK2 also regulates ENaC by a mechanism that does not depend on its kinase activity. We show that a wild-type GRK2 (wtGRK2) and a kinase-dead GRK2 mutant (K220RGRK2), but not a GRK2 mutant that lacks the C-terminal RH domain (ΔRH-GRK2) or a GRK2 mutant that cannot interact with Gαq/11/14 (D110AGRK2), increase activity of ENaC. GRK2 up-regulates the basal activity of the channel as a consequence of its RH domain binding the α-subunits of Gq/11. We further found that expression of constitutively active Gαq/11 mutants significantly inhibits activity of ENaC. Conversely, co-expression of siRNA against Gαq/11 increases ENaC activity. The effect of Gαq on ENaC activity is not due to change in ENaC membrane expression and is independent of Nedd4-2. These findings reveal a novel mechanism by which GRK2 and Gq/11 α-subunits regulate the activity ENaC.

scholarly journals Graft-versus-host disease reduces regulatory T-cell migration into the tumour tissue

Immunology ◽  
2012 ◽  
Vol 137 (1) ◽  
pp. 80-88 ◽  
Author(s):  
Christoph Dürr ◽  
Marie Follo ◽  
Marco Idzko ◽  
Wilfried Reichardt ◽  
Robert Zeiser
Keyword(s):  
Cell Migration ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Regulatory T Cell ◽  
Tumour Tissue ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Migration

scholarly journals Subcellular optogenetic inhibition of G proteins generates signaling gradients and cell migration

2014 ◽  
Vol 25 (15) ◽  
pp. 2305-2314 ◽  
Author(s):  
Patrick R. O'Neill ◽  
N. Gautam
Keyword(s):  
Cell Migration ◽  
G Protein ◽  
Intracellular Signaling ◽  
Signaling Molecules ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Cell Behaviors ◽  
Directed Cell Migration ◽  
Neurite Initiation ◽  
Mechanistic Basis

Cells sense gradients of extracellular cues and generate polarized responses such as cell migration and neurite initiation. There is static information on the intracellular signaling molecules involved in these responses, but how they dynamically orchestrate polarized cell behaviors is not well understood. A limitation has been the lack of methods to exert spatial and temporal control over specific signaling molecules inside a living cell. Here we introduce optogenetic tools that act downstream of native G protein–coupled receptor (GPCRs) and provide direct control over the activity of endogenous heterotrimeric G protein subunits. Light-triggered recruitment of a truncated regulator of G protein signaling (RGS) protein or a Gβγ-sequestering domain to a selected region on the plasma membrane results in localized inhibition of G protein signaling. In immune cells exposed to spatially uniform chemoattractants, these optogenetic tools allow us to create reversible gradients of signaling activity. Migratory responses generated by this approach show that a gradient of active G protein αi and βγ subunits is sufficient to generate directed cell migration. They also provide the most direct evidence so for a global inhibition pathway triggered by Gi signaling in directional sensing and adaptation. These optogenetic tools can be applied to interrogate the mechanistic basis of other GPCR-modulated cellular functions.

334 Pattern of regulatory T-cell migration in AE17 tumour bearing mice following tumour challenge

Cytokine ◽  
2008 ◽  
Vol 43 (3) ◽  
pp. 322-323
Author(s):  
Haydn T. Kissick ◽  
Demelza J. Ireland ◽  
Manfred W. Beilharz
Keyword(s):  
Cell Migration ◽  
T Cell ◽  
Regulatory T Cell ◽  
Tumour Bearing ◽  
T Cell Migration
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