Forskolin-inducible cAMP Pathway Negatively Regulates T-cell Proliferation by Uncoupling the Interleukin-2 Receptor Complex

Rodriguez, Georgialina; Ross, Jeremy A.; Nagy, Zsuzsanna; Kirken, Robert A.

doi:10.1074/jbc.m112.408765

Cited by 39 publications

(42 citation statements)

References 59 publications

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“…These data are consistent with a previous report showing that activation of cAMP signaling in transgenic mice expressing an activated form of cAMP response element binding protein (CREB) increases the in vitro proliferation of primary myoblasts (Stewart et al, 2011), and contrast with the cell cycle inhibitory effects of this chemical in some other systems (e.g. human T cells (Rodriguez et al, 2013) and thyroid cancer cell lines (Yano et al, 2007)). Forskolin does not inhibit satellite cell differentiation in vitro, and forskolin-treated muscle progenitors differentiate normally after removal of the compound or in its continued presence.…”

Section: Discussionsupporting

confidence: 93%

A Zebrafish Embryo Culture System Defines Factors that Promote Vertebrate Myogenesis across Species

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Iovino

et al. 2013

Cell

150

194

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SUMMARY Ex vivo expansion of satellite cells and directed differentiation of pluripotent cells to mature skeletal muscle have proved difficult challenges for regenerative biology. Using a zebrafish embryo culture system with reporters of early and late skeletal muscle differentiation, we examined the influence of 2,400 chemicals on myogenesis and identified six that expanded muscle progenitors, including three GSK3β inhibitors, two calpain inhibitors and one adenylyl cyclase activator, forskolin. Forskolin also enhanced proliferation of mouse satellite cells in culture and maintained their ability to engraft muscle in vivo. A combination of bFGF, forskolin and the GSK3β inhibitor BIO induced skeletal muscle differentiation in human induced pluripotent stem cells (iPSCs) and produced engraftable myogenic progenitors that contributed to muscle repair in vivo. In summary, these studies reveal functionally conserved pathways regulating myogenesis across species and identify chemical compounds that expand mouse satellite cells and differentiate human iPSCs into engraftable muscle.

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Section: Discussionsupporting

confidence: 93%

A Zebrafish Embryo Culture System Defines Factors that Promote Vertebrate Myogenesis across Species

Tabebordbar

Iovino

et al. 2013

Cell

150

194

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“…Future experiments will be needed to determine the extent to which these pathways are engaged during GPR174‐Gαs signaling. Cyclic AMP and PKA can also antagonize STAT5 signaling, which could potentially contribute to GPR174‐mediated repression of IL‐2 responsiveness . Finally, as antagonists of Gαs‐coupled receptors for adenosine and prostaglandin E2 are under consideration as immuno‐oncology agents, studies of GPR174 and LysoPS bioavailability in the context of tumors are warranted.…”

Section: Resultsmentioning

confidence: 99%

Lysophosphatidylserine suppression of T‐cell activation via GPR174 requires Gαs proteins

Barnes

Cyster

2018

Immunol Cell Biol

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G protein-coupled receptors regulate diverse aspects of T-cell activity and effector function. Recently, we showed that GPR174 mediates the suppression of T-cell proliferation in vitro induced by the polar lipid lysophosphatidylserine (LysoPS). Here, we investigated the in vivo activity of this pathway and characterized the mechanisms involved. Using in vivo models of T-cell proliferation induced by sublethal irradiation or regulatory T-cell depletion, we show that GPR174 expression can constrain T-cell proliferation. In vitro experiments established that Gαs G proteins are needed for LysoPS/GPR174-mediated suppression of T-cell proliferation. Mechanistically, LysoPS acts via GPR174 and Gαs to suppress IL-2 production by activated T cells and limit upregulation of the activation markers CD25 and CD69. Together, our findings identify GPR174 as an abundantly expressed Gαs-dependent receptor that can negatively regulate naive T-cell activation. See also: News and Commentary by Robert & Mackay.

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“…cAMP Production Assay cAMP production was detected as previously described [15]. Briefly, B16 cells were treated with 10, 20 or 40 µM cAMP for 30, 60 or 120 min and were maintained at 37°C.…”

Section: Morphology Of B16f1 Cells Treated By Cmsp As Observed By Temmentioning

confidence: 99%

P-Hydroxycinnamaldehyde Induces B16-F1 Melanoma Cell Differentiation via the RhoA-MAPK Signaling Pathway

Zhao

Sun

Han

et al. 2016

Cell Physiol Biochem

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Background/Aims: Due to its antitumor and gastroprotective properties, cochinchina momordica seed (CMS), has been widely used to treat cancer patients in Asia. Our previous reports have shown that CMS is able to induce the differentiation of B16-F1 melanoma cells. However, its functional component and mechanism remain unclear and are addressed in this study. Methods and Results: CMSP (p-hydroxycinnamaldehyde isolated from CMS) inhibited the proliferation, migration and invasiveness of B16-F1 cells both in vivo and in vitro. CMSP also induced the differentiation of B16-F1 cells, as characterized by dendrite-like outgrowth, increased melanogenesis and enhanced tyrosinase activity. Furthermore, CMSP treatment reduced the level of malignant markers of melanoma, specifically S-100B and melanoma-derived growth regulatory protein precursor (MIA), in a concentration-dependent manner. According to a western blot analysis, B16-F1 cells treated with CMSP exhibited a sustained increase in p-P38 and decreased activities of ERK and JNK. Our data further indicated that the downregulation of GTP-RhoA, which was mediated by increased cAMP release, was involved in CMSP-induced changes in MAPK, while LPA (Lysophosphatidic acid) partially reversed CMSP-induced B16 cell differentiation. Conclusion: These results demonstrated that CMSP-induced differentiation of B16F1 cells may occur through the RhoA-MAPK axis, which suggests a new potential strategy for melanoma treatment.

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Forskolin-inducible cAMP Pathway Negatively Regulates T-cell Proliferation by Uncoupling the Interleukin-2 Receptor Complex

Cited by 39 publications

References 59 publications

A Zebrafish Embryo Culture System Defines Factors that Promote Vertebrate Myogenesis across Species

A Zebrafish Embryo Culture System Defines Factors that Promote Vertebrate Myogenesis across Species

Lysophosphatidylserine suppression of T‐cell activation via GPR174 requires Gαs proteins

P-Hydroxycinnamaldehyde Induces B16-F1 Melanoma Cell Differentiation via the RhoA-MAPK Signaling Pathway

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