O-021. Modulation of mammalian sperm adenylyl cyclase by FPP and adenosine involves first stimulatory and then inhibitory adenosine receptors and G proteins

The discovery of mutated, GTPase-deficient alpha subunits of Gs or Gi2 in certain human endocrine tumors has suggested that heterotrimeric G proteins play a role in the oncogenic process. Expression of these altered forms of G alpha s or G alpha i2 proteins in rodent fibroblasts activates or inhibits endogenous adenylyl cyclase, respectively, and causes certain alterations in cell growth. However, it is not clear whether growth abnormalities result from altered cyclic AMP synthesis. In the present study, we asked whether a recently discovered family of G proteins, Gq, which does not affect adenylyl cyclase activity, but instead mediates the activation of phosphatidylinositol-specific phospholipase C harbors transforming potential. We mutated the cDNA for the alpha subunit of murine Gq in codons corresponding to a region involved in binding and hydrolysis of GTP. Similar mutations unmask the transforming potential of p21ras or activate the alpha subunits of Gs or Gi2. Our results show that when expressed in NIH 3T3 cells, activating mutations convert G alpha q into a dominant acting oncogene.

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Regulation of G proteins and adenylyl cyclase in brain regions of caffeine-tolerant and -dependent mice

Brain Research ◽

10.1016/s0006-8993(98)00582-4 ◽

1998 ◽

Vol 804 (1) ◽

pp. 52-62 ◽

Cited By ~ 5

Author(s):

Kimberly A Leite-Morris ◽

Gary B Kaplan ◽

Jonathan G Smith ◽

Mary T Sears

Keyword(s):

Adenylyl Cyclase ◽

G Proteins ◽

Brain Regions

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A2B Adenosine Receptor and Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20205139 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5139 ◽

Cited By ~ 11

Author(s):

Zhan-Guo Gao ◽

Kenneth A. Jacobson

Keyword(s):

G Proteins ◽

Anticancer Agents ◽

Immune Suppression ◽

Adenosine Receptors ◽

Immune Surveillance ◽

G Protein Coupled Receptors ◽

Normal Tissues ◽

Cancer Tissues ◽

G Protein Coupled

There are four subtypes of adenosine receptors (ARs), named A1, A2A, A2B and A3, all of which are G protein-coupled receptors (GPCRs). Locally produced adenosine is a suppressant in anti-tumor immune surveillance. The A2BAR, coupled to both Gαs and Gαi G proteins, is one of the several GPCRs that are expressed in a significantly higher level in certain cancer tissues, in comparison to adjacent normal tissues. There is growing evidence that the A2BAR plays an important role in tumor cell proliferation, angiogenesis, metastasis, and immune suppression. Thus, A2BAR antagonists are novel, potentially attractive anticancer agents. Several antagonists targeting A2BAR are currently in clinical trials for various types of cancers. In this review, we first describe the signaling, agonists, and antagonists of the A2BAR. We further discuss the role of the A2BAR in the progression of various cancers, and the rationale of using A2BAR antagonists in cancer therapy.

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Modification of cardiac β-adrenoceptor mechanisms by H2O2

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.2.h416 ◽

1998 ◽

Vol 274 (2) ◽

pp. H416-H423 ◽

Cited By ~ 4

Author(s):

Sujata Persad ◽

Heinz Rupp ◽

Rashi Jindal ◽

Jugpal Arneja ◽

Naranjan S. Dhalla

Keyword(s):

Oxidative Stress ◽

Signal Transduction ◽

Adenylyl Cyclase ◽

G Proteins ◽

Cardiac Dysfunction ◽

Biochemical Parameters ◽

Adenylyl Cyclase Activity ◽

High Concentrations ◽

Stimulation Of

From the role of oxidative stress in cardiac dysfunction, we investigated the effect of H2O2, an activated species of oxygen, on β-adrenoceptors, G proteins, and adenylyl cyclase activities. Rat heart membranes were incubated with different concentrations of H2O2before the biochemical parameters were measured. Both the affinity and density of β1-adrenoceptors were decreased, whereas the density of the β2-adrenoceptors was decreased and the affinity was increased by 1 mM H2O2. Time- and concentration-dependent biphasic changes in adenylyl cyclase activities in the absence or presence of isoproterenol were observed when membranes were incubated with H2O2; however, activation of the enzyme by isoproterenol was increased or unaltered. The adenylyl cyclase activities in the absence or presence of forskolin, NaF, and Gpp(NH)p were depressed by H2O2. Catalase alone or in combination with mannitol was able to significantly decrease the magnitude of alterations due to H2O2. The cholera toxin-stimulated adenylyl cyclase activity and ADP ribose labeling of Gs proteins were decreased by treatment with 1 mM H2O2, whereas Gi protein activities, as reflected by pertussis toxin-stimulation of adenylyl cyclase and ADP ribosylation, were unaltered. The Gs and Gi protein immunoreactivities, estimated by labeling with respective antibodies, indicate a decrease in binding to the 45-kDa band of Gs protein, whereas no change in the binding of antibodies to the 52-kDa band of Gs protein or the 40-kDa subunit of Gi protein was evident when the membranes were treated with 1 mM H2O2. These results suggest that H2O2in high concentrations may attenuate the β-adrenoceptor-linked signal transduction in the heart by changing the functions of Gs proteins and the catalytic subunit of the adenylyl cyclase enzyme.

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