What question did this study set out to answer?

To investigate the downstream cAMP effectors, specifically protein kinase A (PKA) and Epac, in mediating forskolin-induced macrophage proliferation and cell survival.

September 20, 2005Journal of Biological ChemistryOpen Access

Coordinate Regulation of Forskolin-induced Cellular Proliferation in Macrophages by Protein Kinase A/cAMP-response Element-binding Protein (CREB) and Epac1-Rap1 Signaling

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Authors

UMUma Kant MisraDuke Medical Center SPSalvatore V. PizzoDuke University

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Implication

In vitro study reveals dual involvement of PKA-CREB and Epac1-Rap1 pathways in forskolin-driven macrophage proliferation, highlighting coordinated cAMP signaling mechanisms.

Key Points

To investigate the downstream cAMP effectors, specifically protein kinase A (PKA) and Epac, in mediating forskolin-induced macrophage proliferation and cell survival.
Treated cultured macrophages with forskolin alongside specific inhibitors targeting PKA (H-89) and phosphatidylinositol 3-kinase (LY294002, wortmannin).
Assessed cell proliferation and DNA synthesis via cell counting and [3H]thymidine incorporation assays.
Evaluated signaling interactions and protein activity using Western blotting, immunoprecipitation of Epac1, and CREB gene silencing with RNA interference.
Forskolin treatment enhanced [3H]thymidine uptake and macrophage proliferation, which was substantially suppressed by PKA inhibition via H-89.
Forskolin increased Epac1 and Rap1.GTP levels, promoted Akt phosphorylation via PI3K rather than PKA, and induced Epac1 complex formation with Rap1 and phosphorylated Akt.
Silencing CREB via RNA interference reduced CREB phosphorylation, decreased Akt phosphorylation at Ser-473 and Thr-308, and suppressed forskolin-induced proliferation while promoting anti-apoptotic mechanisms.

Cite This Study

Misra et al. (2005) studied this question.

synapsesocial.com/papers/6a727caa6ceb2bbd16e05fdf https://doi.org/10.1074/jbc.m507332200

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Implication

In vitro study reveals dual involvement of PKA-CREB and Epac1-Rap1 pathways in forskolin-driven macrophage proliferation, highlighting coordinated cAMP signaling mechanisms.

Coordinate Regulation of Forskolin-induced Cellular Proliferation in Macrophages by Protein Kinase A/cAMP-response Element-binding Protein (CREB) and Epac1-Rap1 Signaling

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Implication

Key Points

Cite This Study

Coordinate Regulation of Forskolin-induced Cellular Proliferation in Macrophages by Protein Kinase A/cAMP-response Element-binding Protein (CREB) and Epac1-Rap1 Signaling

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Implication

Key Points

Cite This Study

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