RGS1 Antibodies

Regulator of G-protein signaling 1 (RGS1)

Regulates G protein-coupled receptor signaling cascades, such as signaling downstream of the N-formylpeptide chemoattractant receptors and leukotriene receptors (PubMed:10480894). Inhibits B cell chemotaxis toward CXCL12 (By similarity).

Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form (PubMed:10480894, PubMed:18434541). .

Gene Information

Human
Gene Name:	RGS1
Uniprot:	Q08116
Entrez:	5996

Family

Belongs to:
No superfamily

Alternative Names

1R20Early response protein 1R20; BL34B-cell activation protein BL34; IER1; IR20immediate-early response 1, B-cell specific; regulator of G-protein signaling 1; regulator of G-protein signalling 1

Molecular Weight

Mass (kDA):
23.858 kDA

Genomic Context

Human
Location:	1q31.2
Sequence:	1; NC_000001.11 (192575773..192580024)

Tissue Specificity

Detected in peripheral blood monocytes (PubMed:10480894). Expression is relatively low in B-cells and chronic lymphocytic leukemia B-cells; however, in other types of malignant B-cell such as non-Hodgkin lymphoma and hairy cell leukemia, expression is constitutively high (PubMed:8473738).

Subcellular Localizations

Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, cytosol.

Diseases

• Neoplasms
• Malignant Neoplasms
• Tissue Adhesions
• Celiac Disease
• Sclerosis
• Carcinoma
• Leukemia
• Lymphoma
• Neoplasm Metastasis
• Multiple Sclerosis
• Melanoma
• Immunologic Deficiency Syndromes
• Inflammation

• Burkitt Lymphoma
• Malignant Paraganglionic Neoplasm
• Leukemogenesis
• Lymphatic Metastasis
• Heart Failure
• Diabetes Mellitus
• Diabetes Mellitus, Insulin-dependent

Pathways

• Cell Migration
• Pathogenesis
• Chemotaxis
• Cell Proliferation
• Cell Cycle
• Secretion
• Cell Activation
• Immune Response
• Localization
• Cell Adhesion
• B Cell Activation
• Lymphocyte Migration
• Cell Growth

• Cell Division
• Tissue Development
• Cell Differentiation
• Mating
• Transport
• Lateral Root Formation
• Drought Tolerance

PTMs

• Phosphorylation

• Methylation

Research Areas

• Signal Transduction

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/RGS1

Boster Bio - Best Uses Of The RGS1 Marker

We will be discussing the RGS1 Marker, and the effects of this mutation upon chemokine receptor signaling. We will also talk about the effects of RGS1 Marker upon Gai2, a heterotrimeric Gprotein that is involved in chemokine-gradient sensing. We will also discuss RGS1 Marker's role in inhibiting the activation of effectors and reducing chemokine/S1P receptor signaling.

Gai2 a heterotrimeric form of G-protein

It has been shown that Gai2 regulates the intracellular Ca 2+ flux in response to CXCL1 signaling in neutrophils. To determine the mechanism by which this protein regulates Ca2+ flux, neutrophils were treated with a Ca2+-sensitive drug and flow cytometry was used for measuring fluorescence reflecting calcium flux. The signal analysis lasted 3 min and peak levels of intracellular Ca 2+ flux were determined.

It has been implicated in bleeding and thrombocytopenia, as well as other disorders. It has also been linked to poor platelet quality during storage. CoRP also caused a significant rise in active caspase3 production and ceramide manufacturing. The protein also regulates surface P–selectin expression, activation of aIIbintegrin and activation by aIIbintegrin.

Early studies on cAMP-producing receptors found that a few ligands increased rather than decreased the level. These receptors caused a change in guanine nucleotide binding affinity and made it difficult to find an equivalent 'Gi" G-protein. Martin Rodbell reviewed the information necessary to identify the equivalent adenylyl cyclease-inhibitory "Gi" G-protein.

The purification and identification of a 45kDa polypeptide from rabbit liver enabled the identification of the choleratoxin substrate as well as the transducing protein. These proteins were copurified with a 36-kDa protein. A polypeptide of 8-10 kDa was also discovered to have been overlooked during the purification process due to its rapid mobility on SDS–PAGE. It was also co-purified together with the 35kDa Polypeptide.

Three Ga-subunits are found in the mammalian brain. Two of them are produced via alternative splicing. The third is by posttranslational modified. The two main isoforms of Gao are G12a and G13a. These are involved with heterotrimeric G protein-linked signalling pathways. They also regulate cell responses and shape.

The membrane-associated and cytosolic heterotrimeric G proteins play a role in the transmission receptor signals from heptahelical GPCRs into intracellular effectors. There are four main families of heterotrimeric G proteins in mammalian mammals. The heterotrimeric G-protein orthologs found in Caenorhabditis melanogaster and Caenorhabditis, elegans, are the same. They regulate cell growth and regulate cytoskeletal rearrangements.

It mediates chemokine-gradient sensing

Boster Bio's RGS1 gene was recently found to mediate chemokine induced migration of Jurkat cells. Jurkat cells are a subset of T cells that express very low levels of CCR7. When transfected with CCR7 and RGS1 isoforms, these cells migrate to CCL19. Also, Jurkat cells transfected with RGS1 decreased their migration to CCL19.

The Gai2 G184S mutation can affect both B cell trafficking as well as chemokine signaling. This mutation also affects B cell entry to peripheral lymph nodes and partial capture in the splenic blood pulp. It may serve a different function in B-cell differentiation, but these findings support the role RGS proteins play in chemoattractant signals in B cells.

These studies prove that RGS1 has an essential role in chemokine grading sensing. RGS1 mRNA levels didn't differ in memory CD4 and naive T cells. These results suggest RGS1 may be a key component in determining how immune system responds with different chemokines. RGS1 may therefore represent a new target for drug development.

The RGS1 gene also plays a major role in ligandmediated desensitization. Nonvisual arrestins are recruited by agonist-induced receptor phosphorylation. This nonvisual arrestin recruitment targets the receptor for internalization. Once the receptor has been absorbed, it can either be recycled or sorted by the lysosomes. This is vital to maintain B lymphocyte chemokine sensitivities in a chemokine-rich setting.

These studies also revealed that RGS1 is a novel receptor which mediates chemokine grade sensing. This gene is responsible to inducing chemokine receptors in other organisms and humans. It is involved in receptor/heterotrimeric G-protein coupling and re-assembly. RGS proteins decrease the chance of directed migration by limiting the GTP binding state of Gai subunits.

The function of RGS1 in chemokine sensing was recently demonstrated in a mouse model of spontaneous colitis. In this model, RGS1-/ mice exhibit enhanced B cell migration despite having the absence of Gai2, which opposes the effect of RGS1 on B cells. Mice lacking RGS1 don't have colon pathology and CCL19 response is not affected by RGS1 deficiency.

RGS1 Marker reduces effector activation

Gai2's G184S mutant has been implicated in abnormal B cells responses to chemoattractants. The mutation also leads to alterations in B cell trafficking and partial entrapment in the splenic red pulp. RGS proteins play a key role in chemoattractant signals, coordinating sensitivity mechanisms and desensitization.

The engagement of the chemoattractant receptor triggers heterotrimeric G-protein coupling and functional Gai dissociation from Gbg subunits. This in turn results in downstream effector activation (D-Migration) GTP hydrolysis, which results in termination of signaling, is also an intrinsic property of the Gai Subunits. GTP hydrolysis is inhibited by the RGS1 marker. It reduces the amount of Gai-GTP and Gbg available for activation.

RGS proteins also inhibit Gbg subunit recruit by preventing subsequent engagement of the b-arrestins. RGS proteins play a less important role in activation of cognate ligands when they are high levels. RGS1 markers also decrease B cell activation due to intracellular calcium stimulation by Gbg. RGS proteins can decrease Gbg-mediated desensitization and increase steady-state pathway activation. G184SKI protein in B cells delayed CXCR5, CR7, AKT phosphorylation.

Gai2 G184S Mutation on Chemokine and S1P Receptor Signaling

The role of RGS proteins in B cell retention in LNs is highly dependent on the delicate balance between signals generated by chemokines and S1P receptors. All RGS protein–Gai2 interactions are lost due to the Gai2 G184S mutant. A marked reduction in chemokine-receptor signaling can be caused by the loss RGS proteins in Gai2. RGS protein loss inhibits S1P signaling to downstream affectors.

G184S has a striking effect on B cell chemokine and S1P signaling. These cells require three-fold higher CXCL13 concentration to trigger migration. These results indicate that the threshold for differentiation of B cells is decreased by loss of normal Gai2 regulation. A loss of normal Gai2 regulation can also lead to increased spontaneous motility in B-cells, which can cause impaired response to chemoattractants gradients.

The G184S mutation blocks the binding of RGS proteins and Gai2. The G184S mutation slows down the release of Gai2-GTP in the GDP-bound state because the RGS proteins cannot bind to it. This failure causes a decrease or delay in basal signaling, and an increase in downstream effector engagement.

This mutation also affects B cell trafficking and chemokine secretion in the lymphatic organs. Gai2 plays a critical role in the proper organization of lymph vessels. Loss of the G184S mutation of Gai2 will have a profound impact upon B cell proliferation as well as chemokine release. It will be fascinating to study the role Gai2 plays in the regulation B cell chemoattractant-signaling in the body.

Ex vivo NET formation assays. Neutrophils were isolated from BMs and stimulated by increasing levels of fMLP. G184S mice had comparable levels of CD11b expression than WT mice. These data also suggest that Gai2 is involved in neutrophil trafficking.

The G184S neutrophils have abnormally altered directional migration. G184S Neutrophils migrate outside of cremaster blood vessels, but they do so within the interstitial area. They also have multiple lamellipodia, but no clear uropod. Further, morphological analysis revealed that individual cells have disorganized leading and trailing edges.