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It is well known that the control of gene expression involves activation of protein kinase cascades that regulate transcription factors within the nucleus.1 The cyclic AMP response element binding protein (CREB) is one of the best characterized stimulus-induced transcription factors.2 This transcription factor is a component of intracellular signaling events that regulate a wide range of biological functions, from spermatogenesis to circadian rhythms and memory.3,4 A variety of protein kinases including protein kinase A (PKA), mitogen-activated protein kinases (MAPKs), and Ca2+/calmodulin-dependent protein kinases (CaMKs) phosphorylate CREB at serine 133 (Ser133), and phosphorylation of Ser133 is required for CREB-mediated transcription.5,6
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1. Transcriptional control by protein phosphorylation: Signal transmission from the cell surface to the nucleus. Curr. Biol. 5(7), 747-757 (1995).
2. Transcriptional regulation by cyclic AMP. Annu. Rev. Biochem. 66, 807-822 (1997).
3. CREB: A stimulus-
4. CREB and memory. Annu. Rev. Neurosci. 21, 127-148 (1998).
5. What turns CREB on? Cell. Signal. 16(11), 1211-1227 (2004).
6. CREB transcriptional activity in neurons is regulated by multiple, calcium-