cell surface bile acid receptor signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by binding of a bile acid to a receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:bf, PMID:12419312, PMID:19442546]

The cell surface bile acid receptor signaling pathway is a complex and crucial mechanism that plays a vital role in regulating various physiological processes, including lipid metabolism, glucose homeostasis, and inflammation. This pathway is initiated by the binding of bile acids, steroidal molecules produced in the liver, to specific receptors located on the cell surface. These receptors, primarily belonging to the G protein-coupled receptor (GPCR) family, are known as the G protein-coupled bile acid receptor 1 (GPBAR1) and the Takeda G protein-coupled receptor 5 (TGR5).

Upon binding to their respective receptors, bile acids trigger a cascade of intracellular signaling events. GPBAR1, also known as the ileal bile acid binding protein (IBABP), primarily activates the G protein Gi, leading to inhibition of adenylyl cyclase and a decrease in intracellular cyclic AMP (cAMP) levels. This reduction in cAMP triggers downstream signaling pathways, including activation of the mitogen-activated protein kinase (MAPK) cascade and phosphorylation of the transcription factor cAMP response element-binding protein (CREB). These events ultimately lead to the modulation of gene expression and the regulation of various cellular processes.

TGR5, on the other hand, preferentially couples to the G protein Gs, resulting in the activation of adenylyl cyclase and an increase in intracellular cAMP levels. This elevation in cAMP activates downstream signaling pathways, including protein kinase A (PKA) and the exchange protein directly activated by cAMP (EPAC). These pathways regulate various cellular functions, such as the release of hormones, such as glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK), as well as the modulation of inflammatory responses.

The cell surface bile acid receptor signaling pathway has far-reaching implications for human health. Dysregulation of this pathway has been linked to various metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Furthermore, the pathway plays a critical role in regulating gut microbiota composition and function, which is essential for maintaining intestinal health and immune function.

In conclusion, the cell surface bile acid receptor signaling pathway is a sophisticated system that integrates the detection of bile acids with the modulation of various cellular processes. Understanding the intricacies of this pathway is crucial for developing novel therapeutic strategies to target metabolic and inflammatory diseases.'
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Proteins (1)

Compounds (55)