Figure 6.

Protein kinase A (PKA) signaling pathway. The majority of G-protein coupled receptors (GPCR) are associated with activation of distinctive adenylate cyclases (ACs) to regulate intracellular cAMP levels. When active, AC produces the second messenger cAMP in response to a wide range of signal-transduction pathways. The main target of cAMP is PKA. Some of the major substrates of PKA include GSK3. PKA phosphorylates and inactivates GSK3, preventing neurodegeneration. PKA also phosphorylates the transcription factor CREB, which in turn allows the recruitment of the coactivator CREB-binding protein (CBP). Thus, PKA is important for an increasing number of physiological processes, such as regulation of the cell cycle that involves chromatin condensation and decondensation. Apart from PKA, other direct targets of cAMP include PDE, p70S6K/RPS6KB1 and PLA2. Pathway objects and links are described separately in Supplementary Figure 16.