| Description |
The transcription factor CREB binds the cyclic AMP response element (CRE) and activates transcription in response to a variety of extracellular signals including cAMP, membrane depolarization, increased intracellular Ca++, and growth and neurotrophic factors (13) (Figure 1). Phosphorylation of CREB at Ser133 regulates the ability of CREB to activate transcription when bound at a CRE. Mutation of Ser133 renders CREB nonresponsive to multiple signaling pathways. A variety of protein kinases have been shown to phosphorylate CREB at Ser133 in vitro, including PKA, PKC, CAM kinase II and IV, and p90rsk. Phosphorylation at Ser133 has also been shown to promote interaction with a CREB binding protein, CBP, required for transcriptional activation by CREB, AP-1, and SRF dependent promoters (3,4). CREB appears to play an important role in learning and memory in both flies and mice. Mice lacking CREB exhibit deficiencies in spatial learning tasks, while flies overexpressing and lacking CREB show
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