Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
The prevailing view of stimulus-induced activation of the transcription factor cAMP response element-binding protein (CREB) presumes phosphorylation at serine-133. Although, phosphorylation of this residue seems to be necessary, it is not sufficient to trigger CREB-driven transcription, indicating that other phosphoserine-133-independent mechanisms are required for full activation of CREB. One of these additional regulatory mechanisms influencing the transcriptional state of CREB may involve multiple phosphorylation events on other phosphoacceptor sites in the protein. This review focuses on the phosphorylation modifications of CREB by distinct protein kinases and discusses the possible implications for the function of CREB.