High resolution

Module 4: Figure CREB activation

Activation of the cyclic AMP response element-binding protein (CREB).

Cyclic AMP response element-binding protein (CREB) is phosphorylated by a number of signalling pathways that employ different kinases to phosphorylate the critical residue Ser-133, which is essential for its transcriptional activity. In addition to activating CREB within the nucleus, some of these signalling pathways also regulate the activity of cofactors called transducers of regulated CREB (TORCs). Under resting conditions, TORC is phosphorylated and resides in the cytoplasm, but upon dephosphorylation, it enters the nucleus, where it acts together with CREB to promote transcription. TORC phosphorylation depends upon a Ca2+-dependent dephosphorylation mediated by calcineurin (CaN) and the cyclic AMP/protein kinase A (PKA)-dependent inhibition of the salt-inducible kinase 2 (SIK2) that phosphorylates TORC.