cross-receptor inhibition within G protein-coupled receptor heterodimer

Definition

Target type: biologicalprocess

Inhibition of one protomer of a G protein-coupled receptor (GPCR) heterodimer by the associated subunit. For example, agonist activation of one cytokine receptor can prevent activation of its associated cytokine receptor subunit. [GOC:al, GOC:bf, PMID:15979374]

Cross-receptor inhibition, a phenomenon occurring within G protein-coupled receptor (GPCR) heterodimers, involves the modulation of signaling by one GPCR subunit upon binding of a ligand to the other subunit. This complex interplay between receptors is a vital aspect of GPCR signaling, contributing to the fine-tuning of cellular responses. In essence, the binding of a ligand to one receptor can alter the signaling properties of the other, often resulting in a decrease or inhibition of its signaling activity.

The mechanism behind cross-receptor inhibition is multifaceted and can involve various molecular interactions. One common mechanism is the alteration of receptor conformation. Upon ligand binding, one receptor subunit may undergo a conformational change that influences the conformation of the other subunit, potentially leading to its destabilization or reduced affinity for its own ligand. This conformational change can also affect the interaction of the heterodimer with downstream signaling molecules, such as G proteins.

Another mechanism involves competition for shared signaling pathways. GPCR heterodimers may share downstream signaling pathways, and the activation of one receptor subunit can lead to the sequestration or inactivation of signaling molecules required for the activation of the other subunit. This competition for shared resources can effectively inhibit the signaling of the second receptor.

Furthermore, cross-receptor inhibition can be mediated by the interaction of the two receptors with accessory proteins. These proteins, such as arrestins or scaffolding proteins, can bind to both receptor subunits, influencing their stability, trafficking, or interaction with signaling molecules. This can result in a decrease in the signaling activity of one receptor due to the influence of the other.

Cross-receptor inhibition plays a crucial role in regulating cellular responses to various stimuli. By modulating the activity of GPCR heterodimers, it allows for the integration of multiple signals and the fine-tuning of cellular responses to specific conditions. This phenomenon has implications for a wide range of physiological processes, including neurotransmission, hormone signaling, and immune responses.

Examples of cross-receptor inhibition can be observed in various systems, such as the regulation of dopamine signaling in the brain or the modulation of insulin sensitivity in peripheral tissues. Understanding the mechanisms and consequences of cross-receptor inhibition is essential for developing novel therapeutic strategies targeting GPCRs, particularly in the context of diseases involving altered GPCR signaling.'
"

Proteins (2)

Compounds (2)