Transcription factor CREB binds the cyclic AMP response element (CRE) and activates transcription in response to a variety of extracellular signals including neurotransmitters, hormones, membrane depolarization, and growth and neurotrophic factors. Protein kinase A and the calmodulin-dependent protein kinases CaMKII stimulate CREB phosphorylation at Ser133, a key regulatory site controlling transcriptional activity (1,2). Growth and neurotrophic factors also stimulate CREB phosphorylation at Ser133 (4). Phosphorylation occurs at Ser133 via p44/42 MAP kinase and p90RSK and also via p38 MAP kinase and MSK1 (5–7). 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 or lacking CREB show enhanced or diminished learning, respectively (8–10). Nonphosphorylated CREB Control Cell Extracts: Total cell extracts from SK-N-MC cells prepared without treatment serve as a negative control. Supplied in SDS Sample Buffer. Phosphorylated CREB Control Cell Extracts: Total cell extracts from SK-N-MC cells prepared with IBMX and forskolin treatment serve as a positive control. Supplied in SDS Sample Buffer.