Isolation and Characterization of Glucocorticoid- and Cyclic AMP-Induced Genes in T Lymphocytes

Harrigan, Maureen T.; Baughman, Gail; Campbell, Naomi F.; Bourgeois, Suzanne

doi:10.1128/mcb.9.8.3438-3446.1989

Cited by 39 publications

(1 citation statement)

References 61 publications

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“…G protein-coupled receptor 83 (GPR83), first identified in murine thymoma cells as a receptor upregulated after treatment with the glucocorticoid dexamethasone (Harrigan et al, 1989;Harrigan et al, 1991;Wang et al, 2001), was later found to exhibit expression in the brain (Pesini et al, 1998;Brezillon et al, 2001). Studies reported robust GPR83 expression in regions involved in modulation of food intake (Muller et al, 2013b;Lueptow et al, 2018;Mack et al, 2019) and reward behaviors (Pesini et al, 1998;Lueptow et al, 2018;Fakira et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

GPR83 Engages Endogenous Peptides from Two Distinct Precursors to Elicit Differential Signaling

et al. 2022

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PEN is an abundant neuropeptide that activates G protein-coupled receptor 83 (GPR83), which is considered a novel therapeutic target due to its roles in regulation of feeding-, reward-, and anxietyrelated behaviors. The major form of PEN in the brain is 22 residues in length. Previous studies have identified shorter forms of PEN in mouse brain and neuroendocrine cells; these shorter forms were named PEN18, PEN19, and PEN20, with the number reflecting the length of the peptide. The C-terminal five residues of PEN20 are identical to the C-terminus of a procholecystokinin (proCCK)derived peptide, named proCCK56-62, that is present in mouse brain. ProCCK56-62 is highly conserved across species, although it has no homology to the bioactive cholecystokinin domain. ProCCK56-62 and a longer form, proCCK56-63, were tested for their ability to engage GPR83. Both peptides bind GPR83 with high affinity, activate second messenger pathways, and induce ligand-mediated receptor endocytosis. Interestingly, the shorter PEN peptides, ProCC56-62 and ProCCK56-63, differentially activate signal transduction pathways. Whereas PEN22 and PEN20 facilitate receptor coupling to Gai, PEN18, PEN19, and ProCCK peptides facilitate coupling to Gas. Furthermore, the ProCCK peptides exhibit dose-dependent Ga subtype selectivity in that they facilitate coupling to Gas at low concentrations and Gai at high concentrations. These data demonstrate that peptides derived from two distinct peptide precursors can differentially activate GPR83 and that GPR83 exhibits Ga subtype preference depending on the nature and concentration of the peptide. These results are consistent with the emerging idea that endogenous neuropeptides function as biased ligands. SIGNIFICANCE STATEMENTWe found that peptides derived from procholecystokinin (proCCK) bind and activate G protein-coupled receptor 83, which is known to bind peptides derived from proSAAS. Different forms of the proCCK-and proSAAS-derived peptides show biased agonism, activating Gas or Gai depending on the length of the peptide and/or its concentration.

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Section: Introductionmentioning

confidence: 99%

GPR83 Engages Endogenous Peptides from Two Distinct Precursors to Elicit Differential Signaling

et al. 2022

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Programmed cell death and Bcl-2 protection in the absence of a nucleus.

1994

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The molecular basis of programmed cell death (PCD) is unknown. An important clue is provided by the Bcl‐2 protein, which can protect many cell types from PCD, although it is not known where or how it acts. Nuclear condensation, DNA fragmentation and a requirement for new RNA and protein synthesis are often considered hallmarks of PCD. We show here, however, that anucleate cytoplasts can undergo PCD and that Bcl‐2 and extracellular survival signals can protect them, indicating that, in some cases at least, the nucleus is not required for PCD or for Bcl‐2 or survival factor protection. We propose that PCD, like the cell cycle, is orchestrated by a cytoplasmic regulator that has multiple intracellular targets.

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Apoptosis induced by anticancer drugs

1992

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Most of the cytotoxic anticancer drugs in current use have been shown to induce apoptosis in susceptible cells. The fact that disparate agents, which interact with different targets, induce cell death with some common features (endonucleolytic cleavage of DNA, changes in chromatin condensation) suggests that cytotoxicity is determined by the ability of the cell to engage this so-called 'programmed' cell death. The mechanism of the coupling of a stimulus (drug-target interaction) to a response (cell death) is not known, but modulation of this coupling may affect the outcome of drug treatment. This review surveys the recent evidence which supports the idea that the drug-target interaction per se is not the sole determinant of cellular sensitivity of cytotoxic drugs. Studies of the signals which might engage apoptosis, the genes which modulate it and the biochemical process of drug-induced apoptosis itself are described, where possible, for glucocorticoids, topoisomerase inhibitors, alkylating agents, antimetabolites and antihormones. It is suggested that identification of the gene products which couple the stimulus to the response, and so determine intrinsic cellular sensitivity (and resistance), will be important targets for new types of drugs. These might then allow responses to occur in the major cancers of man, which are chemoresistant.

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Isolation and Characterization of Glucocorticoid- and Cyclic AMP-Induced Genes in T Lymphocytes

Cited by 39 publications

References 61 publications

GPR83 Engages Endogenous Peptides from Two Distinct Precursors to Elicit Differential Signaling

GPR83 Engages Endogenous Peptides from Two Distinct Precursors to Elicit Differential Signaling

Programmed cell death and Bcl-2 protection in the absence of a nucleus.

Apoptosis induced by anticancer drugs

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