On the Cover

The cover shows a model of CREB regulation by calcium influx and cAMP in PC12 cells. Calcium influx via L-type channels (left) stimulates CREB-dependent transcription via activation of a PKA-dependent Rap1-ERK pathway. The requirement for this pathway probably reflects a role for ERK signaling in calcium-induced CREB phosphorylation. Elevation of intracellular cAMP levels (right) also stimulates CREB function through the PKA-dependent Rap1-ERK pathway. In this case, cAMP phosphorylates CREB directly via PKA and utilizes the Rap1-ERK pathway to stimulate a component downstream of CBP recruitment. This latter step may reflect an action of ERK signaling on CBP function. Details can be found in the article by Grewal et al., pages 34433-34441.34433