G-Protein Receptor Kinases (grKs) Play an Important Regulatory Role in the K/BxN Serum Transfer Model of Inflammatory Arthritis

2007 ◽  
Vol 119 (1) ◽  
pp. S234-S235
Author(s):  
T.K. Tarrant ◽  
R.R. Rampersad ◽  
C.G. Moore ◽  
L.R. Rothlein ◽  
R.M. Lefkowitz ◽  
...  
Keyword(s):  
G Protein ◽  
Inflammatory Arthritis ◽  
Regulatory Role ◽  
Transfer Model ◽  
Protein Receptor ◽  
Serum Transfer ◽  
Receptor Kinases ◽  
Serum Transfer Model

scholarly journals Neutrophil-derived leukotriene B4 is required for inflammatory arthritis

2006 ◽  
Vol 203 (4) ◽  
pp. 837-842 ◽  
Author(s):  
Mei Chen ◽  
Bing K. Lam ◽  
Yoshihide Kanaoka ◽  
Peter A. Nigrovic ◽  
Laurent P. Audoly ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Leukotriene B4 ◽  
Transfer Model ◽  
Effector Functions ◽  
Serum Transfer ◽  
Cellular Source ◽  
Disease Induction ◽  
Deficient Mice ◽  
Arthritis Susceptibility ◽  
Serum Transfer Model

Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption.

Upregulation of G protein-linked receptor kinases with advancing age in rat aorta

2001 ◽  
Vol 280 (3) ◽  
pp. R897-R903 ◽  
Author(s):  
William E. Schutzer ◽  
John F. Reed ◽  
Michael Bliziotes ◽  
Scott L. Mader
Keyword(s):  
G Protein ◽  
Rat Aorta ◽  
Aortic Tissue ◽  
Fischer 344 Rats ◽  
Membrane Expression ◽  
Fischer 344 ◽  
Age Related ◽  
Protein Receptor ◽  
Receptor Kinases ◽  
Increased Activity

The age-related decline in β-adrenergic receptor (β-AR)-mediated vasorelaxation is associated with desensitization of β-ARs without significant downregulation. The primary mode of this homologous β-AR desensitization, in general, is via G protein receptor kinases (GRK). Therefore, we hypothesize that age-related changes in GRKs are causative to this etiology in rat aorta. Herein, we investigate the activity and cellular distribution (cytoplasmic vs. membrane) of several GRK isoforms and β-arrestin proteins. GRK activity was assessed in extracts from aortic tissue of 6-wk, 6-mo, 12-mo, and 24-mo-old male Fischer-344 rats using a rhodopsin phosphorylation assay. We also performed immunoblots on lysates from aorta with specific antibodies to GRK-2, -3, -5, and β-arrestin-1. Results show an age-related increase in GRK activity. Furthermore, expression of GRK-2 (cytoplasmic and membrane), GRK-3 (cytoplasmic and membrane), and β-arrestin (soluble) increased with advancing age, whereas GRK-5 (membrane) expression remained unchanged. These results suggest that age is associated with increased activity and expression of specific GRKs. This increase likely results in enhanced phosphorylation and desensitization of β-ARs. These biochemical changes are consistent with observed aging physiology.

scholarly journals TRANCE/RANKL Knockout Mice Are Protected from Bone Erosion in a Serum Transfer Model of Arthritis

2001 ◽  
Vol 159 (5) ◽  
pp. 1689-1699 ◽  
Author(s):  
Allison R. Pettit ◽  
Hong Ji ◽  
Dietrich von Stechow ◽  
Ralph Müller ◽  
Steven R. Goldring ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Bone Erosion ◽  
Transfer Model ◽  
Serum Transfer ◽  
Serum Transfer Model

scholarly journals G-protein receptor kinases 2, 5 and 6 redundantly modulate Smoothened-GATA transcriptional crosstalk in fetal mouse hearts

2018 ◽  
Vol 121 ◽  
pp. 60-68 ◽  
Author(s):  
Antonietta Franco ◽  
Lihong Zhang ◽  
Scot J. Matkovich ◽  
Attila Kovacs ◽  
Gerald W. Dorn
Keyword(s):  
G Protein ◽  
Fetal Mouse ◽  
Protein Receptor ◽  
Receptor Kinases

G-Protein-coupled Receptors: Regulatory Role of Receptor Kinases and Arrestin Proteins

1992 ◽  
Vol 57 (0) ◽  
pp. 127-133 ◽  
Author(s):  
R.J. Lefkowitz ◽  
J. Inglese ◽  
W.J. Koch ◽  
J. Pitcher ◽  
H. Attramadal ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Regulatory Role ◽  
Receptor Kinases ◽  
G Protein Coupled

scholarly journals Desensitization of the Neurokinin-1 Receptor (NK1-R) in Neurons: Effects of Substance P on the Distribution of NK1-R, Gαq/11, G-Protein Receptor Kinase-2/3, and β-Arrestin-1/2

1998 ◽  
Vol 9 (8) ◽  
pp. 2305-2324 ◽  
Author(s):  
Karen McConalogue ◽  
Carlos U. Corvera ◽  
Patrick D. Gamp ◽  
Eileen F. Grady ◽  
Nigel W. Bunnett
Keyword(s):  
Plasma Membrane ◽  
Substance P ◽  
G Protein ◽  
Neurokinin 1 Receptor ◽  
Protein Receptor ◽  
Early Endosomes ◽  
Receptor Kinases ◽  
Neurokinin 1 ◽  
G Protein Coupled ◽  
Neurotransmitter Substance

Observations in reconstituted systems and transfected cells indicate that G-protein receptor kinases (GRKs) and β-arrestins mediate desensitization and endocytosis of G-protein–coupled receptors. Little is known about receptor regulation in neurons. Therefore, we examined the effects of the neurotransmitter substance P (SP) on desensitization of the neurokinin-1 receptor (NK1-R) and on the subcellular distribution of NK1-R, Gαq/11, GRK-2 and -3, and β-arrestin-1 and -2 in cultured myenteric neurons. NK1-R was coexpressed with immunoreactive Gαq/11, GRK-2 and -3, and β-arrestin-1 and -2 in a subpopulation of neurons. SP caused 1) rapid NK1-R–mediated increase in [Ca2+]i, which was transient and desensitized to repeated stimulation; 2) internalization of the NK1-R into early endosomes containing SP; and 3) rapid and transient redistribution of β-arrestin-1 and -2 from the cytosol to the plasma membrane, followed by a striking redistribution of β-arrestin-1 and -2 to endosomes containing the NK1-R and SP. In SP-treated neurons Gαq/11 remained at the plasma membrane, and GRK-2 and -3 remained in centrally located and superficial vesicles. Thus, SP induces desensitization and endocytosis of the NK1-R in neurons that may be mediated by GRK-2 and -3 and β-arrestin-1 and -2. This regulation will determine whether NK1-R–expressing neurons participate in functionally important reflexes.

scholarly journals Evolution of the shut-off steps of vertebrate phototransduction

Open Biology ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 170232 ◽  
Author(s):  
Trevor D. Lamb ◽  
Hardip R. Patel ◽  
Aaron Chuah ◽  
David M. Hunt
Keyword(s):  
G Protein ◽  
Whole Genome Duplication ◽  
Genome Duplication ◽  
Parallel Evolution ◽  
Whole Genome ◽  
Gene Expansion ◽  
Protein Receptor ◽  
Receptor Kinases ◽  
Rod And Cone Photoreceptors ◽  
Ancestral Vertebrate

Different isoforms of the genes involved in phototransduction are expressed in vertebrate rod and cone photoreceptors, providing a unique example of parallel evolution via gene duplication. In this study, we determine the molecular phylogeny of the proteins underlying the shut-off steps of phototransduction in the agnathan and jawed vertebrate lineages. For the G-protein receptor kinases (GRKs), the GRK1 and GRK7 divisions arose prior to the divergence of tunicates, with further expansion during the two rounds of whole-genome duplication (2R); subsequently, jawed and agnathan vertebrates retained different subsets of three isoforms of GRK. For the arrestins, gene expansion occurred during 2R. Importantly, both for GRKs and arrestins, the respective rod isoforms did not emerge until the second round of 2R, just prior to the separation of jawed and agnathan vertebrates. For the triplet of proteins mediating shut-off of the G-protein transducin, RGS9 diverged from RGS11, probably at the second round of 2R, whereas Gβ5 and R9AP appear not to have undergone 2R expansion. Overall, our analysis provides a description of the duplications and losses of phototransduction shut-off genes that occurred during the transition from a chordate with only cone-like photoreceptors to an ancestral vertebrate with both cone- and rod-like photoreceptors.

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