CBP or CREB-binding protein is a nuclear transcriptional coactivator protein that binds specifically to the PKA-phosphorylated form of the CREB protein. Microinjection of an anti-CBP antiserum into fibroblasts leads to inhibition of transcription from a cAMP promoter. CBP can also cooperates with upstream activators, such as JUN. When JUN is phosphorylated at the transcriptionally stimulatory sites ser73 and ser63, it binds CBP with comparable affinity to CREB. Insulin signaling may directly regulate many cAMP signaling pathways at the transcriptional level by controlling CBP recruitment. Mutant CBP can be aberrantly recruited to CREB protein, resulting in inappropriate activation of gluconeogenesis and glucose intolerance.