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.

The KDM Inhibitor GSKJ4 Triggers CREB Downregulation via a Protein Kinase A and Proteasome-Dependent Mechanism in Human Acute Myeloid Leukemia Cells

“…It is largely known that PKA, as well as other kinases such as ERK1/2, can phosphorylate CREB protein at serine 133 residue (45)(46)(47)(48). Moreover, phosphorylation at Ser133 is also involved in CREB protein stability (40,41,44).…”

“…Among the others kinases, ERK1/2 and PKA play a key role in CREB phosphorylation at Ser133 residue (45)(46)(47)(48). To test the possible involvement of ERK1/2 pathway on GSKJ4-mediated Ser133 phosphorylation induction and CREB protein decrease, we treated U-937 cells with GSKJ4 up to 24 h in presence or in absence of the upstream ERK1/2 inhibitor PD98059.…”

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

“…However, the passage of NGF across the BBB represents a major challenge for nonviral gene delivery via a systematic transvascular route. Therefore, the delivery of this therapy is limited to invasive intracerebral injection [ 135 ]. Nonetheless, its efficiency is also questionable.…”

Exogenous NAD+ Stimulates MUC2 Expression in LS 174T Goblet Cells via the PLC-Delta/PTGES/PKC-Delta/ERK/CREB Signaling Pathway

“…Therefore, conservation of an intact mucus layer that properly regulates immune responses is a main factor that is necessary for the maintenance of intestinal homeostasis and the prevention of intestinal inflammatory diseases.MUC2 gene expression is regulated by cyclic AMP (cAMP) response element-binding protein (CREB) in retinoic acid-treated normal human tracheobronchial epithelial (NHTBE) cells [4]. CREB is a transcription factor regulating the expression of genes involved in a variety of cellular processes, such as cell growth and survival, differentiation, and mucin production [5]. Upon cAMP-induced phosphorylation through intracellular signaling cascades, CREB is activated and stimulates gene transcription by binding to the promoters of target genes.…”

“…Upon cAMP-induced phosphorylation through intracellular signaling cascades, CREB is activated and stimulates gene transcription by binding to the promoters of target genes. CREB phosphorylation through the mitogen-activated protein kinase (MAPK) signaling pathway is associated with various human diseases [5]. For example, angiotensin II induces cardiac fibrosis by enhancing periostin expression via the p38 MAPK-CREB pathway [6].…”