Roles of Cyclic AMP Response Element Binding Activation in the ERK1/2 and p38 MAPK Signalling Pathway in Central Nervous System, Cardiovascular System, Osteoclast Differentiation and Mucin and Cytokine Production

Abstract

There are many downstream targets of mitogen-activated protein kinase (MAPK) signalling that are involved in neuronal development, cellular differentiation, cell migration, cancer, cardiovascular dysfunction and inflammation via their functions in promoting apoptosis and cell motility and regulating various cytokines. It has been reported that cyclic AMP response element-binding protein (CREB) is phosphorylated and activated by cyclic AMP signalling and calcium/calmodulin kinase. Recent evidence also points to CREB phosphorylation by the MAPK signalling pathway. However, the specific roles of CREB phosphorylation in MAPK signalling have not yet been reviewed in detail. Here, we describe the recent advances in the study of this MAPK-CREB signalling axis in human diseases. Overall, the crosstalk between extracellular signal-related kinase (ERK) 1/2 and p38 MAPK signalling has been shown to regulate various physiological functions, including central nervous system, cardiac fibrosis, alcoholic cardiac fibrosis, osteoclast differentiation, mucin production in the airway, vascular smooth muscle cell migration, steroidogenesis and asthmatic inflammation. In this review, we focus on ERK1/2 and/or p38 MAPK-dependent CREB activation associated with various diseases to provide insights for basic and clinical researchers.