GPSM2 Serves as an Independent Prognostic Biomarker for Liver Cancer Survival

Background and Objective: Liver cancer is a malignancy with a poor prognosis. G protein signaling modulator 2 is mainly related to cell division and cell cycle regulation. In this review, the relationship between G protein signaling modulator 2 and clinical characteristics of patients with liver cancer has been explored, especially with respect to its prognostic value. Methods: G protein signaling modulator 2 messenger RNA expression and clinicopathological characteristics of patients with liver cancer were obtained from The Cancer Genome Atlas. The expression level of G protein signaling modulator 2 RNA-Seq was validated by using Gene Expression Omnibus. Chi-square test was performed to evaluate the relationship between G protein signaling modulator 2 expression and clinical characteristics. The threshold value of G protein signaling modulator 2 in the diagnosis of liver cancer was evaluated by a receiver–operating characteristic curve. Cox regression analysis and Kaplan-Meier curves were performed to evaluate the relationship between G protein signaling modulator 2 and liver cancer prognosis, which included overall and residual-free survival, and explored the prognostic value of G protein signaling modulator 2. Liver cancer survival analyses were validated by using the data of G protein signaling modulator 2 RNA-Seq from the International Cancer Genome Consortium. Results: The expression level of G protein signaling modulator 2 messenger RNA was remarkably higher in liver cancer than that in healthy tissues ( P < 2.2 × e−16), which was also validated by data from the GSE14520 database. In addition, high G protein signaling modulator 2 expression significantly correlated with histological grade ( P = .020), vital status ( P < .001), clinical ( P = .001), and T stage ( P = .001). The receiver–operating characteristic curves showed G protein signaling modulator 2 to be an advantageous diagnostic molecule for liver cancer (area under curve = 0.893). Furthermore, the results of Cox analysis and Kaplan-Meier curves suggested that the upregulation of G protein signaling modulator 2 expression is linked to poor prognosis and G protein signaling modulator 2 messenger RNA could be an independent predictor for liver cancer, which was validated by data from the International Cancer Genome Consortium database. Conclusions: G protein signaling modulator 2 messenger RNA was overexpressed in liver cancer, and G protein signaling modulator 2 is an independent prognostic factor. G protein signaling modulator 2 is expected to be a treatment target for cancer.

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Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1701529114 ◽

2017 ◽

Vol 114 (10) ◽

pp. 2562-2567 ◽

Cited By ~ 132

Author(s):

Thomas J. Cahill ◽

Alex R. B. Thomsen ◽

Jeffrey T. Tarrasch ◽

Bianca Plouffe ◽

Anthony H. Nguyen ◽

...

Keyword(s):

G Protein ◽

Receptor Internalization ◽

G Protein Signaling ◽

Mutant Form ◽

Protein Signaling ◽

The Core ◽

Loop Region ◽

Relationship Of ◽

The Relationship ◽

G Protein Coupled

β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize G protein signaling, to initiate signaling on their own, and to mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR–βarr complexes: the “tail” conformation, with βarr primarily coupled to the phosphorylated GPCR C-terminal tail, and the “core” conformation, where, in addition to the phosphorylated C-terminal tail, βarr is further engaged with the receptor transmembrane core. However, the relationship of these distinct conformations to the various functions of βarrs is unknown. Here, we created a mutant form of βarr lacking the “finger-loop” region, which is unable to form the core conformation but retains the ability to form the tail conformation. We find that the tail conformation preserves the ability to mediate receptor internalization and βarr signaling but not desensitization of G protein signaling. Thus, the two GPCR–βarr conformations can carry out distinct functions.

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A novel regulator of G-protein signaling bearing GAP activity for Gαi and Gαq in megakaryocytes

Blood ◽

10.1182/blood.v97.10.3051 ◽

2001 ◽

Vol 97 (10) ◽

pp. 3051-3060 ◽

Cited By ~ 40

Author(s):

Yuka Nagata ◽

Masaaki Oda ◽

Hiroko Nakata ◽

Yuka Shozaki ◽

Tohru Kozasa ◽

...

Keyword(s):

G Protein ◽

Messenger Rna ◽

G Protein Signaling ◽

Protein Signaling ◽

Hematopoietic Stem ◽

Α Subunit ◽

Isolation And Characterization ◽

Guanosine Triphosphatase ◽

Immunohistochemical Studies

Abstract The regulator of G-protein signaling (RGS) negatively regulates the α subunit of G proteins by accelerating their intrinsic guanosine triphosphatase (GTPase) activity. Here are reported the isolation and characterization of a novel mouse RGS, termed RGS18, which is a new member of RGS subfamily B. Northern blot analysis showed that RGS18 messenger RNA was detected predominantly in spleen and hematopoietic cells, and immunohistochemical studies demonstrated that RGS18 was expressed in megakaryocytes, platelets, granulocytes/monocytes, and, weakly, in hematopoietic stem cells, but not in lymphocytes or erythrocytes. Although various subcellular localizations of RGS have been reported, RGS18 was found to be localized in cytoplasm in megakaryocytes. In vitro binding assays of RGS18 with megakaryocyte cell lysates with or without AlF4− treatment demonstrated that RGS18 specifically binds to 2 α subunits of the G protein, Gαi and Gαq. Furthermore, RGS18 clearly exhibited GTPase-activating protein (GAP) activity for Gαi and Gαq but not for Gαs or Gα12. In addition, chemokine stromal-derived factor 1 (SDF-1), which has been reported to stimulate megakaryocyte colony formation in the presence of thrombopoietin, affected the binding of RGS18 to Gαi but not to Gαq. Therefore, the newly isolated RGS18 turned out to be a new member of the RGS family bearing GAP activity for Gαi, which might be stimulated by SDF-1 in megakaryocytes, as well as for Gαq. Thus, RGS18 may play an important role in proliferation, differentiation, and/or migration of megakaryocytes.

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