Neurokinin B Induces c-fos Transcription via Protein Kinase C and Activation of Serum Response Factor and Elk-1 in Immortalized GnRH Neurons

Glidewell-Kenney, Christine; Trang, Crystal; Shao, Paul P.; Gutierrez‐Reed, Navarre; Uzo-Okereke, Adaku M.; Coss, Djurdjica; Mellon, Pamela L.

doi:10.1210/en.2014-1263

Cited by 13 publications

(9 citation statements)

References 44 publications

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“…A heterologous cell culture-expressing Tac3 receptor confirmed its identity and specificity as Nkb receptor, which was demonstrated by the clear preference for Nkb and Nkf over the other neurokinins, NKA and SP. When activated, Tac3r can utilize both PKA and PKC signal transduction pathways, as also reported for other species (Biran et al 2012, Glidewell-Kenney et al 2014. As for the antagonists, interestingly SB222200, the widely used non-peptide mammalian NK3R antagonist (Sarau et al 2000, Malherbe et al 2011, was non-potent on the STB Tac3r, suggesting that SB222200 is acting through a non-conserved region within the receptor.…”

Section: Discussionmentioning

confidence: 56%

Neurokinin B regulates reproduction via inhibition of kisspeptin in a teleost, the striped bass

Zmora

Wong

Stubblefield

et al. 2017

Journal of Endocrinology

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Kisspeptin and neurokinin B (NKB) are neuropeptides co-expressed in the mammalian hypothalamus and coordinately control GnRH signaling. We have found that Nkb and kisspeptin neurons are distinct in the teleost, striped bass (STB) and capitalized on this phenomenon to study the mode of action of Nkb and its related neuropeptide-F (Nkf), both of which are encoded by the gene. brain slices and administration studies revealed that Nkb/f consistently downregulated, whereas antagonist (AntD) administration restored this effect. Overall, a minor effect was noted on expression, whereas Gnrh1 content in the pituitaries was reduced after Nkb/f treatment and increased with AntD. Concomitantly, immunostaining demonstrated that hypothalamic Nkb neurons border and densely innervate the largest kiss2 neuronal population in the hypothalamus, which also coexpresses Nkb receptor. No expression of Nkb receptor or Nkb neuronal projections was detected near/in Gnrh1 soma in the preoptic area. At the level of the pituitary, however, the picture was more complex: both Nkb/f and AntD upregulated and expression and Lh secretion Together with the stimulatory effect of Nkb/f on Lh/Fsh secretion from pituitary cells, , this may indicate an additional independent action of Nkb/f within the pituitary, in which the hypothalamic pathway is more dominant. The current study demonstrates that Nkb/f utilizes multiple pathways to regulate reproduction in the STB and that in the brain, Nkb mainly acts as a negative modulator of kiss2 to regulate the release of Gnrh1.

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Section: Discussionmentioning

confidence: 56%

Neurokinin B regulates reproduction via inhibition of kisspeptin in a teleost, the striped bass

Zmora

Wong

Stubblefield

et al. 2017

Journal of Endocrinology

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“…The connection between a rise in cytoplasmic Ca 2+ and an up‐regulation of c‐Fos gene transcription is accomplished by protein kinases, and MAPKs, PKC and Ca 2+ /calmodulin‐dependent protein kinases have been proposed to function as signal transducers (Johnson et al ., ; Dolmetsch et al ., ; Ely et al ., ; Glidewell‐Kenney et al ., ). The experiments described in this study shed light on the importance of MAPKs in the regulation of c‐Fos expression by a TRPM3‐induced signalling cascade.…”

Section: Discussionmentioning

confidence: 97%

“…As TCF activation is required, together with an SRF dimer, to activate transcription via the SRE, other cryptic TCF binding sites within the c‐Fos promoter may compensate for the mutation of the Ets site 5´ of the CArG box. Alternatively, Elk‐1 may be recruited to the c‐Fos promoter via protein–protein interaction with SRF, as described recently for the GnRH‐induced activation of c‐Fos expression in gonadotropes (Ely et al ., ) or the neurokinin B‐stimulated c‐Fos transcription in immortalized GnRH neurons (Glidewell‐Kenney et al ., ). This scenario would explain the biological effects of the Elk‐1 mutant REST/Elk‐1∆C reported in this study, which retains the B‐domain of Elk‐1 and therefore interfered with the Elk‐1–SRF interaction.…”

Section: Discussionmentioning

confidence: 97%

“…The nature of the Ca 2+ source determines which genetic elements, transcription factors and protein kinases are required to activate c‐Fos expression (Gallin and Greenberg, ). In previous studies, Ca 2+ influx was induced either by activating voltage‐gated Ca 2+ channels, ionotropic NMDA receptors and Gαq‐coupled receptors or by adding Ca 2+ ionophores to the cells (Sheng et al ., ; Lee and Gilman, ; Misra et al ., ; Thompson et al ., ; Xia et al ., ; Johnson et al ., ; Ely et al ., ; Glidewell‐Kenney et al ., ). Here, we have identified the signalling molecules that connect TRPM3 Ca 2+ channel stimulation with enhanced c‐Fos expression.…”

Section: Introductionmentioning

confidence: 97%

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CREB, AP‐1, ternary complex factors and MAP kinases connect transient receptor potential melastatin‐3 (TRPM3) channel stimulation with increased c‐Fos expression

Rubil

Rößler

Thiel

2015

British J Pharmacology

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BACKGROUND AND PURPOSE The rise in intracellular Ca 2+ stimulates the expression of the transcription factor c-Fos. Depending on the mode of entry of Ca 2+ into the cytosol, distinct signal transducers and transcription factors are required. Here, we have analysed the signalling pathway connecting a Ca 2+ influx via activation of transient receptor potential melastatin-3 (TRPM3) channels with enhanced c-Fos expression. EXPERIMENTAL APPROACH Transcription of c-Fos promoter/reporter genes that were integrated into the chromatin via lentiviral gene transfer was analysed in HEK293 cells overexpressing TRPM3. The transcriptional activation potential of c-Fos was measured using a GAL4-c-Fos fusion protein. KEY RESULTS The signalling pathway connecting TRPM3 stimulation with enhanced c-Fos expression requires the activation of MAP kinases. On the transcriptional level, three Ca 2+-responsive elements, the cAMP-response element and the binding sites for the serum response factor (SRF) and AP-1, are essential for the TRPM3-mediated stimulation of the c-Fos promoter. Ternary complex factors are additionally involved in connecting TRPM3 stimulation with the up-regulation of c-Fos expression. Stimulation of TRPM3 channels also increases the transcriptional activation potential of c-Fos. CONCLUSIONS AND IMPLICATIONS Signalling molecules involved in connecting TRPM3 with the c-Fos gene are MAP kinases and the transcription factors CREB, SRF, AP-1 and ternary complex factors. As c-Fos constitutes, together with other basic region leucine zipper transcription factors, the AP-1 transcription factor complex, the results of this study explain TRPM3-induced activation of AP-1 and connects TRPM3 with the biological functions regulated by AP-1. Abbreviations AP-1, activator protein-1; bZIP, basic region leucine zipper; CREB, cAMP-response element-binding protein; SRE, serum response element; SRF, serum response factor; TCF, ternary complex factor; TPA, phorbol 12-myristate 13-acetate; TRP, transient receptor potential BJP British Journal of Pharmacology

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“…ETS-domain containing protein (Elk1), a transcription factor belonging to the ETS oncogene family, regulates the oncogene c-fos by phosphorylation through activation of the PKC/ERK pathways (5)(6)(7)(8). Studies have reported that Elk1 has roles in cell proliferation, the cell cycle, apoptosis and tumorigenesis (9,10).…”

Section: Introductionmentioning

confidence: 99%

Suppression of Elk1 inhibits thyroid cancer progression by mediating PTEN expression

Kong

Yin

et al. 2018

Oncol Rep

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ETS‑domain containing protein (Elk1) is reported to be a member of the ETS oncogene family, and promotes tumorigenesis in cancer such as bladder, prostate and ovarian. Nevertheless, the role of Elk1 in thyroid cancer progression remains unclear. In the present study, we aimed to investigate the role and underlying molecular mechanism of Elk1 in thyroid cancer. The results indicated that Elk1 was significantly upregulated in thyroid cancer tissues and cells. We found that loss of Elk1 function obviously induced the expression of early growth response‑1 (Egr‑1) and PTEN, promoted apoptosis and constrained the proliferation of thyroid cancer cells. Furthermore, Egr‑1 inhibition obviously abrogated the induction of PTEN induced by Elk1 reduction. Moreover, Egr‑1 suppression prevented the promotion of apoptosis and the inhibition of cell proliferation caused by Elk1 reduction. In conclusion, Elk1 inhibition induced thyroid cancer cell apoptosis and restrained their proliferation by regulating Egr‑1/PTEN, indicating a potential role for Elk1 in thyroid cancer treatment.

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Neurokinin B Induces c-fos Transcription via Protein Kinase C and Activation of Serum Response Factor and Elk-1 in Immortalized GnRH Neurons

Cited by 13 publications

References 44 publications

Neurokinin B regulates reproduction via inhibition of kisspeptin in a teleost, the striped bass

Neurokinin B regulates reproduction via inhibition of kisspeptin in a teleost, the striped bass

CREB, AP‐1, ternary complex factors and MAP kinases connect transient receptor potential melastatin‐3 (TRPM3) channel stimulation with increased c‐Fos expression

Suppression of Elk1 inhibits thyroid cancer progression by mediating PTEN expression

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