Epac Activation Converts cAMP from a Proliferative into a Differentiation Signal in PC12 Cells

• DOI: 10.1091/mbc.e05-05-0432
• Publication Date: 2005-10-06T00:33:17Z
• Authors: Simone Kiermayer; Ricardo M. Biondi; Jochen Imig; Guido Plotz; Jörg Haupenthal; Stefan Zeuzem; Albrecht Piiper
• Keywords: Signal pathway

Elevation of the intracellular cAMP concentration ([cAMP]i) regulates metabolism, cell proliferation, and differentiation plays roles in memory formation neoplastic growth. mediates its effects mainly through activation protein kinase A (PKA) as well Epac1 Epac2, exchange factors activating small GTPases Rap1 Rap2. However, how utilizes these effectors to induce distinct biological responses is unknown. We here studied specific PKA Epac neuroendocrine PC12 cells. In cells, elevation [cAMP]i activates extracellular signal-regulated (ERK) 1/2 induces low-degree neurite outgrowth. The present study showed that stimulation triggered ERK1/2 was considerably more transient than observed upon simultaneous both Epac. Unexpectedly, PKA-specific analog induced proliferation rather proliferative signaling pathway activated by involved epidermal growth factor receptor ERK1/2. Activation appeared extend duration PKA-dependent converted from a into an anti-proliferative, outgrowth-promoting signal. Thus, outcome can depend heavily on set activated.