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Shayo, C. et al.

Shayo, Legnazzi, Monczor, Fernández, Riveiro, Baldi, Davio,

The time-course of cyclic AMP signaling is critical for leukemia U-937 cell differentiation.

The regulation of the cAMP signaling is intimately involved in several cellular processes, including cell differentiation. Here, we provide strong evidence supporting that the time-course of cAMP signal is critical for leukemia U-937 cell differentiation. Three stimulating-cAMP agents were used to analyze the correlation between cAMP time-course and cell differentiation. All three agents denoted similar cAMP maximal responses in dose-response experiments. The kinetic of desensitization showed differential characteristics, while H2 receptor desensitized homologously without affecting PGE2 or forskolin effect, PGE2 response showed mixed desensitization characterized by a homologous initial phase followed by a heterologous phase. Regarding forskolin, long-term stimuli attenuated PGE2 and H2 agonist response without affecting adenylyl cyclase activity. In the absence of phosphodiesterase inhibitors, the three agents induced similar maximal cAMP levels after 5 min, but only that induced by the H2 agonist returned to basal levels. Consistent with this observation, H2 agonist was not able to induce U-937 cell maturation in contrast to PGE2 and forskolin, supporting the importance of time-course signaling in the determination of cell behavior.[1]

References

The time-course of cyclic AMP signaling is critical for leukemia U-937 cell differentiation. Shayo, C., Legnazzi, B.L., Monczor, F., Fernández, N., Riveiro, M.E., Baldi, A., Davio, C. Biochem. Biophys. Res. Commun. (2004) [Pubmed]

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