2013
DOI: 10.1074/jbc.m112.408765
|View full text |Cite
|
Sign up to set email alerts
|

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

Abstract: Background: Within activated T-cells, the binding of IL-2 to its receptor initiates the Jak3/Stat5 cascade culminating in proliferation. Results: Elevated levels of cAMPi within activated T-cells suppresses proliferation by targeting multiple levels of the IL-2R cascade. Conclusion: Cross-talk occurs between cAMP/PKA and the IL-2R/Jak3/Stat5 cascade in human T-cells. Significance: Therapeutic potential exists in manipulating the described cross-talk for the treatment of various immune diseases.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

4
38
0

Year Published

2013
2013
2024
2024

Publication Types

Select...
8
1

Relationship

1
8

Authors

Journals

citations
Cited by 39 publications
(42 citation statements)
references
References 59 publications
4
38
0
Order By: Relevance
“…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%
“…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%
“…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%
“…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%