Protein kinase A – cAMP response element-binding protein pathway (PKA–CREB pathway)

The **Protein kinase A – CREB pathway** is a canonical signal transduction pathway in which **cyclic AMP-dependent protein kinase A (PKA)** phosphorylates the **cAMP response element-binding protein (CREB)** at Ser133, activating its transcription factor function[1][3][4][5]. Activated CREB recruits the co-activators **CBP/p300**, enabling transcription of genes involved in **cell growth, survival, differentiation, metabolism, immune regulation, and neuronal plasticity**[1][3]. Dysregulation of this pathway contributes to tumorigenesis by promoting proliferation, resisting apoptosis, and enabling immune evasion, and also plays key roles in neuronal and hematopoietic physiology[2][6][5]. Targeting the PKA–CREB–CBP interface is considered a promising but challenging therapeutic strategy, with small molecules such as KG-501 and naphthol derivatives explored experimentally[2][4]. The pathway is often measured by assessing CREB phosphorylation and activity, which serve as potential biomarkers in multiple disease contexts[4][6][5].\n\n**Note:** The request for information about "Protein kinase A – CREB pathway" does not refer to a single molecular entity, but rather a signaling axis composed of **multiple proteins** (enzyme and transcription factor), making direct mapping to the conventions for drug targets difficult. In structured databases, separate entries exist for "Protein kinase A" (PKA) and "cAMP response element-binding protein" (CREB), not the pathway as a whole.

Other names

PKA–CREB pathwaycAMP–PKA–CREB signalingcAMP response element-binding protein pathwaycAMP-dependent protein kinase–CREB pathway

Direct inhibition of CREB–CBP/p300 interaction, blocking transcriptional coactivator recruitment - Inhibition of CREB phosphorylation at Ser133 via PKA antagonists - Modulation of cAMP signaling upstream (Adenosine receptor antagonism) - Inhibition of CREB–DNA binding, blocking downstream gene transcription - Promoting CREB protein degradation