G protein-coupled receptor signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane. [GOC:bf, GOC:mah, PMID:16902576, PMID:24568158, Wikipedia:G_protein-coupled_receptor]

G protein-coupled receptor (GPCR) signaling is a ubiquitous and vital process in cellular communication. It involves a series of intricate steps initiated by the binding of a ligand, such as a hormone, neurotransmitter, or odorant molecule, to a GPCR located on the cell surface.

1. **Ligand Binding and Receptor Activation:** The ligand binds to its specific GPCR, inducing a conformational change in the receptor. This change activates the receptor's intracellular domain, exposing a binding site for a heterotrimeric G protein.

2. **G Protein Activation:** The activated GPCR interacts with the G protein, causing the alpha subunit of the G protein to exchange GDP for GTP. This GTP binding activates the alpha subunit, triggering its dissociation from the beta and gamma subunits.

3. **Signaling Cascade:** The activated alpha subunit, carrying GTP, interacts with downstream effector proteins, such as adenylyl cyclase or phospholipase C, initiating a signaling cascade.

4. **Second Messenger Production:** Effector proteins generate second messengers, which act as intracellular signaling molecules. For example, adenylyl cyclase produces cyclic AMP (cAMP), while phospholipase C produces inositol trisphosphate (IP3) and diacylglycerol (DAG).

5. **Cellular Responses:** Second messengers activate various intracellular pathways, leading to a wide array of cellular responses, including changes in gene expression, enzyme activity, ion channel permeability, and cellular morphology.

6. **Signal Termination:** The GTP bound to the alpha subunit is hydrolyzed to GDP by an intrinsic GTPase activity. This inactivation of the alpha subunit causes it to reassociate with the beta and gamma subunits, reforming the inactive heterotrimeric G protein. The GPCR also undergoes desensitization, preventing further signaling.

GPCR signaling is highly diverse, with different GPCRs mediating specific cellular responses. This diversity is achieved through the combination of various ligands, G protein subtypes, effector proteins, and second messenger systems.

GPCR signaling plays crucial roles in a wide range of physiological processes, including:

- **Nervous system function:** Neurotransmission, sensory perception, and mood regulation.
- **Hormonal regulation:** Metabolism, growth, and development.
- **Immune system function:** Inflammation and immune response.
- **Cardiovascular system:** Heart rate, blood pressure, and vascular tone.
- **Gastrointestinal system:** Digestion and nutrient absorption.

Dysregulation of GPCR signaling can lead to various diseases, including cancer, cardiovascular diseases, neurological disorders, and metabolic disorders. Understanding the intricacies of GPCR signaling pathways is essential for developing novel therapeutic strategies targeting these diseases.'
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Proteins (216)

Compounds (6,693)